LENALIDOMIDE HEMIHYDRATE

Details

Stereochemistry	RACEMIC
Molecular Formula	2C13H13N3O3.H2O
Molecular Weight	536.5365
Optical Activity	( + / - )
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.NC1=CC=CC2=C1CN(C3CCC(=O)NC3=O)C2=O.NC4=CC=CC5=C4CN(C6CCC(=O)NC6=O)C5=O

InChI

InChIKey=OTJHSDXKMBRCMM-UHFFFAOYSA-N

InChI=1S/2C13H13N3O3.H2O/c2*14-9-3-1-2-7-8(9)6-16(13(7)19)10-4-5-11(17)15-12(10)18;/h2*1-3,10H,4-6,14H2,(H,15,17,18);1H2

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C13H13N3O3
Molecular Weight	259.2606
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021880s039s040lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22966948 http://www.revlimidrems.com/

Lenalidomide (trade name Revlimid) is a derivative of thalidomide introduced in 2004. It is an immunomodulatory agent with anti-angiogenic properties. Revlimid in combination with dexamethasone is indicated for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. Also is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. In addition, Revlimid is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. The mechanism of action of lenalidomide remains to be fully characterized. Lenalidomide inhibited the secretion of pro-inflammatory cytokines and increased the secretion of anti-inflammatory cytokines from peripheral blood mononuclear cells. Lenalidomide causes a delay in tumor growth in some in vivo nonclinical hematopoietic tumor models including multiple myeloma. Immunomodulatory properties of lenalidomide include activation of T cells and natural killer (NK) cells, increased numbers of NKT cells, and inhibition of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. In multiple myeloma cells, the combination of lenalidomide and dexamethasone synergizes the inhibition of cell proliferation and the induction of apoptosis. Recently was discovered, that protein cereblon (CRBN) is a proximate, therapeutically important molecular target of lenalidomide. Low CRBN expression was found to correlate with drug resistance in multiple myeloma (MM) cell lines and primary MM cells. One of the downstream targets of CRBN identified is interferon regulatory factor 4 (IRF4), which is critical for myeloma cell survival and is down-regulated by (immune-modulatory drugs) treatment. CRBN is also implicated in several effects of immunomodulatory drugs, such as down-regulation of tumor necrosis factor-α (TNF-α) and T cell immunomodulatory activity, demonstrating that the pleotropic actions of the immunomodulatory drugs (IMiDs) are initiated by binding to CRBN. Future dissection of CRBN downstream signaling will help to delineate the underlying mechanisms for IMiD action and eventually lead to development of new drugs with more specific anti-myeloma activities. It may also provide a biomarker to predict IMiD response and resistance. Lenalidomide also inhibited the expression of cyclooxygenase-2 (COX-2) but not COX-1 in vitro.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Protein cereblon 10 Target ID: Q96SW2 Gene ID: 51185.0 Gene Symbol: CRBN Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=22552008	Inhibitor 8297		3.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Multiple myeloma 159 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021880s039s040lbl.pdf	Primary	Approved 8429	REVLIMID Approved Use REVLIMID is a thalidomide analogue indicated for the treatment of patients with: Multiple myeloma (MM), in combination with dexamethasone (1.1). Transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities (1.2). Mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib (1.3). Limitations of Use: REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials (1.4). 1.1 Multiple Myeloma REVLIMID in combination with dexamethasone is indicated for the treatment of patients with multiple myeloma (MM). 1.2 Myelodysplastic Syndromes REVLIMID is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. 1.3 Mantle Cell Lymphoma REVLIMID is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. 1.4 Limitations of Use: REVLIMID is not indicated and is not recommended for the treatment of patients with CLL outside of controlled clinical trials [see Warnings and Precautions (5.5) Launch Date 2005
Mantle cell lymphoma 24 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021880s039s040lbl.pdf	Primary	Approved 8429	REVLIMID Approved Use REVLIMID is a thalidomide analogue indicated for the treatment of patients with: Multiple myeloma (MM), in combination with dexamethasone (1.1). Transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities (1.2). Mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib (1.3). Limitations of Use: REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials (1.4). 1.1 Multiple Myeloma REVLIMID in combination with dexamethasone is indicated for the treatment of patients with multiple myeloma (MM). 1.2 Myelodysplastic Syndromes REVLIMID is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. 1.3 Mantle Cell Lymphoma REVLIMID is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. 1.4 Limitations of Use: REVLIMID is not indicated and is not recommended for the treatment of patients with CLL outside of controlled clinical trials [see Warnings and Precautions (5.5) Launch Date 2005
Myelodysplastic syndromes 58 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021880s039s040lbl.pdf	Primary	Approved 8429	REVLIMID Approved Use REVLIMID is a thalidomide analogue indicated for the treatment of patients with: Multiple myeloma (MM), in combination with dexamethasone (1.1). Transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities (1.2). Mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib (1.3). Limitations of Use: REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials (1.4). 1.1 Multiple Myeloma REVLIMID in combination with dexamethasone is indicated for the treatment of patients with multiple myeloma (MM). 1.2 Myelodysplastic Syndromes REVLIMID is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. 1.3 Mantle Cell Lymphoma REVLIMID is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. 1.4 Limitations of Use: REVLIMID is not indicated and is not recommended for the treatment of patients with CLL outside of controlled clinical trials [see Warnings and Precautions (5.5) Launch Date 2005

C_max

Value	Dose	Co-administered	Analyte	Population
433.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29411269	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LENALIDOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1252.08 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02538965	2 mg/kg single, oral dose: 2 mg/kg route of administration: oral experiment type: single co-administered:		LENALIDOMIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:

AUC

Value	Dose	Co-administered	Analyte	Population
1472.4 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29411269	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LENALIDOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5378.83 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02538965	2 mg/kg single, oral dose: 2 mg/kg route of administration: oral experiment type: single co-administered:		LENALIDOMIDE plasma	Homo sapiens population: unhealthy age: Children sex: food status:

T_1/2

Value	Dose	Co-administered	Analyte	Population
3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29411269	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LENALIDOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/5fa97bf5-28a2-48f1-8955-f56012d296be/spl-doc?hl=lenalidomide			LENALIDOMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
25 mg 1 times / day multiple, oral Highest studied dose Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32829079	unhealthy, 35 years (range: 20-70years) n = 3 Health Status: unhealthy Condition: Relapsed or Refractory Classical Hodgkin Lymphoma Age Group: 35 years (range: 20-70years) Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/32829079	Sources: https://pubmed.ncbi.nlm.nih.gov/32829079
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021880lbl.pdf	pregnant, adult Health Status: pregnant Age Group: adult Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021880lbl.pdf	Other AEs: Birth defects... Other AEs: Birth defects (serious) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021880lbl.pdf
10 mg 1 times / day steady, oral (starting) Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_MedR.pdf Page: p. 101	unhealthy, adult n = 395 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 395 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_MedR.pdf Page: p. 101	Disc. AE: Thrombocytopenia, Neutropenia... AEs leading to discontinuation/dose reduction: Thrombocytopenia (6.1%) Neutropenia (3.5%) Rash (2%) Nausea (1.5%) Diarrhea (1.3%) Fatigue (1%) Anaemia NOS (1%) Abdominal distension (1%) Pyrexia (0.8%) Dyspnea (0.8%) Cough (0.5%) Abdominal pain NOS (0.5%) Face edema (0.5%) Pruritus (0.5%) Anemia hemolytic (NOS) (0.5%) Pneumonia NOS (1%) Arthralgia (0.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_MedR.pdf Page: p. 101
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021880lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021880lbl.pdf	Other AEs: Neutropenia, Thrombocytopenia... Other AEs: Neutropenia Thrombocytopenia Thrombosis venous deep Pulmonary embolism Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021880lbl.pdf
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00109772	unhealthy n = 87 Health Status: unhealthy Condition: Complex Regional Pain Syndrome Population Size: 87 Sources: https://clinicaltrials.gov/ct2/show/NCT00109772	Other AEs: Joint sprain, Foot fracture... Other AEs: Joint sprain (serious, 2 patients) Foot fracture (serious, 1 patient) Thrombosis (serious, 1 patient) Blood human chorionic gonadotropin positive (serious, 1 patient) Blood potassium decreased (serious, 1 patient) Pregnancy test false positive (serious, 1 patient) Sick sinus syndrome (serious, 1 patient) Pregnancy NOS (serious, 2 patients) Abortion spontaneous NOS (serious, 1 patient) Pain NOS (serious, 1 patient) Arthritis NOS (serious, 1 patient) Angioneurotic edema (serious, 1 patient) Rash NOS (below serious, 24 patients) Pruritus (below serious, 8 patients) Dry skin (below serious, 6 patients) Diarrhoea NOS (below serious, 11 patient) Constipation (below serious, 8 patients) Vomiting NOS (below serious, 5 patients) Dizziness (below serious, 9 patients) Pyrexia (below serious, 6 patients) Nasopharyngitis (below serious, 6 patients) Pharyngitis (below serious, 6 patients) Sinusitis NOS (below serious, 5 patients) Alanine aminotransferase increased (below serious, 5 patients) Cramp muscle (below serious, 5 patients) Insomnia (below serious, 7 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00109772
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00179621	unhealthy n = 69 Health Status: unhealthy Condition: Myelodysplastic Syndrome Population Size: 69 Sources: https://clinicaltrials.gov/ct2/show/NCT00179621	Other AEs: Fatigue, General physical health deterioration... Other AEs: Fatigue (serious, 1 patient) General physical health deterioration (serious, 2 patients) Mucosal inflammation (serious, 1 patient) Pneumonia (serious, 3 patients) Anal abscess (serious, 1 patient) Bacteraemia (serious, 1 patient) Cellulitis (serious, 1 patient) Erysipelas (serious, 1 patient) Gastroenteritis (serious, 1 patient) Pneumonia legionella (serious, 1 patient) Pyelonephritis (serious, 1 patient) Septic shock (serious, 2 patients) Urinary tract infection (serious, 1 patient) Epistaxis (serious, 1 patient) Lung disorder (serious, 1 patient) Pulmonary embolism (serious, 2 patients) Acute myeloid leukaemia (serious, 8 patients) Bladder cancer (serious, 1 patient) Breast cancer (serious, 1 patient) Colon cancer (serious, 1 patient) Colorectal cancer (serious, 1 patient) Histiocytosis haematophagic (serious, 1 patient) Refractory anaemia with an excess of blasts (serious, 2 patients) Confusional state (serious, 1 patient) Delirium (serious, 1 patient) Altered mood (serious, 1 patient) Acute myocardial infarction (serious, 2 patients) Cardiac failure (serious, 1 patient) Myocardial infarction (serious, 1 patient) Tachyarrhythmia (serious, 1 patient) Abdominal pain (serious, 1 patient) Abdominal pain upper (serious, 1 patient) Colitis (serious, 1 patient) Constipation (serious, 1 patient) Diarrhoea (serious, 3 patients) Intestinal obstruction (serious, 1 patient) Femoral neck fracture (serious, 1 patient) Humerus fracture (serious, 1 patient) Spinal compression fracture (serious, 1 patient) Subdural haematoma (serious, 1 patient) Synovial rupture (serious, 1 patient) Hyperglycaemia (serious, 1 patient) Cerebral haemorrhage (serious, 1 patient) Cerebrovascular accident (serious, 1 patient) Coma (serious, 1 patient) Headache (serious, 1 patient) Colic renal (serious, 1 patient) Renal failure (serious, 1 patient) Stress urinary incontinence (serious, 1 patient) Deep vein thrombosis (serious, 4 patients) Arterial occlusive disease (serious, 1 patient) Hypotension (serious, 1 patient) Orthostatic hypotension (serious, 1 patient) Anaemia (serious, 1 patient) Autoimmune thrombocytopenia (serious, 1 patient) Bone marrow failure (serious, 1 patient) Febrile neutropenia (serious, 2 patients) Haemolysis (serious, 1 patient) Neutropenia (serious, 5 patients) Pancytopenia (serious, 1 patient) Splenomegaly (serious, 1 patient) Thrombocytopenia (serious, 3 patients) Arthritis (serious, 1 patient) Back pain (serious, 2 patients) Joint range of motion decreased (serious, 1 patient) Musculoskeletal pain (serious, 1 patient) Skin ulcer (serious, 1 patient) Urticaria (serious, 1 patient) Diarrhoea (below serious, 37 patients) Nausea (below serious, 21 patient) Constipation (below serious, 19 patients) Abdominal pain (below serious, 14 patients) Vomiting (below serious, 9 patients) Dry mouth (below serious, 5 patients) Abdominal pain upper (below serious, 8 patients) Dyspepsia (below serious, 5 patients) Flatulence (below serious, 1 patient) Fatigue (below serious, 17 patients) Oedema peripheral (below serious, 13 patients) Pyrexia (below serious, 16 patients) Influenza like illness (below serious, 5 patients) Oedema (below serious, 4 patients) Pain (below serious, 4 patients) Neutropenia (below serious, 57 patients) Leukopenia (below serious, 8 patients) Thrombocytopenia (below serious, 36 patients) Nasopharyngitis (below serious, 16 patients) Upper respiratory tract infection (below serious, 12 patients) Urinary tract infection (below serious, 12 patients) Bronchitis (below serious, 14 patients) Cystitis (below serious, 4 patients) Lower respiratory tract infection (below serious, 5 patients) Respiratory tract infection (below serious, 3 patients) Sinusitis (below serious, 6 patients) Gastroenteritis (below serious, 6 patients) Influenza (below serious, 5 patients) Pharyngitis (below serious, 4 patients) Rhinitis (below serious, 3 patients) Headache (below serious, 14 patients) Dizziness (below serious, 10 patients) Sciatica (below serious, 4 patients) Balance disorder (below serious, 4 patients) Peripheral sensory neuropathy (below serious, 1 patient) Muscle spasms (below serious, 15 patients) Back pain (below serious, 8 patients) Myalgia (below serious, 6 patients) Arthralgia (below serious, 5 patients) Pain in extremity (below serious, 10 patients) Musculoskeletal chest pain (below serious, 5 patients) Neck pain (below serious, 3 patients) Decreased appetite (below serious, 8 patients) Iron overload (below serious, 5 patients) Hypoalbuminaemia (below serious, 1 patient) Hypokalaemia (below serious, 3 patients) Hypomagnesaemia (below serious, 3 patients) Cough (below serious, 10 patients) Dyspnoea (below serious, 9 patients) Epistaxis (below serious, 4 patients) Dyspnoea exertional (below serious, 3 patients) Oropharyngeal pain (below serious, 6 patients) Pruritus (below serious, 20 patients) Dry skin (below serious, 10 patients) Rash (below serious, 12 patients) Alopecia (below serious, 4 patients) Hyperhidrosis (below serious, 4 patients) Petechiae (below serious, 4 patients) Insomnia (below serious, 9 patients) Anxiety (below serious, 5 patients) Contusion (below serious, 4 patients) Fall (below serious, 4 patients) Joint sprain (below serious, 1 patient) Wound (below serious, 4 patients) Alanine aminotransferase increased (below serious, 5 patients) Weight decreased (below serious, 5 patients) Haematoma (below serious, 6 patients) Phlebitis (below serious, 4 patients) Hypertension (below serious, 9 patients) Cataract (below serious, 5 patients) Conjunctivitis (below serious, 5 patients) Dysuria (below serious, 3 patients) Vertigo (below serious, 3 patients) Musculoskeletal pain (below serious, 11 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT00179621
15 mg 1 times / day steady, oral Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01021423	unhealthy n = 4 Health Status: unhealthy Condition: Mantle Cell Lymphoma Population Size: 4 Sources: https://clinicaltrials.gov/ct2/show/NCT01021423	Other AEs: Squamous cell carcinoma, Herpes zoster... Other AEs: Squamous cell carcinoma (serious, 1 patient) Herpes zoster (below serious, 1 patient) Herpes zoster ophthalmic (below serious, 1 patient) Viral rash (below serious, 1 patient) Thrombocytopenia (below serious, 1 patient) Neutropenia (below serious, 1 patient) Constipation (below serious, 1 patient) Abdominal pain upper (below serious, 1 patient) Diarrhoea (below serious, 1 patient) Dry mouth (below serious, 1 patient) Flatulence (below serious, 1 patient) Stomatitis (below serious, 1 patient) Chills (below serious, 1 patient) Oedema peripheral (below serious, 1 patient) Dysgeusia (below serious, 1 patient) Peripheral sensory neuropathy (below serious, 1 patient) Eczema (below serious, 1 patient) Rash (below serious, 1 patient) Conjunctivitis (below serious, 1 patient) Muscle spasms (below serious, 1 patient) Neck pain (below serious, 1 patient) Basal cell carcinoma (below serious, 1 patient) Malignant melanoma (below serious, 1 patient) Libido decreased (below serious, 1 patient) Erectile dysfunction (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01021423
25 mg 1 times / day steady, oral Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02041325	unhealthy n = 22 Health Status: unhealthy Condition: Plasma Cell Dyscrasias Population Size: 22 Sources: https://clinicaltrials.gov/ct2/show/NCT02041325	Other AEs: Bleeding, Ischemic colitis... Other AEs: Bleeding (serious, 1 patient) Ischemic colitis (serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02041325
5 mg 1 times / day steady, oral Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00179621	unhealthy n = 69 Health Status: unhealthy Condition: Myelodysplastic Syndrome Population Size: 69 Sources: https://clinicaltrials.gov/ct2/show/NCT00179621	Other AEs: Pyrexia, Generalised oedema... Other AEs: Pyrexia (serious, 5 patients) Generalised oedema (serious, 1 patient) Non-cardiac chest pain (serious, 1 patient) Pneumonia (serious, 5 patients) Erysipelas (serious, 1 patient) Gastroenteritis (serious, 1 patient) Infection (serious, 1 patient) Lower respiratory tract infection (serious, 1 patient) Respiratory tract infection (serious, 1 patient) Staphylococcal sepsis (serious, 1 patient) Urinary tract infection (serious, 3 patients) Urosepsis (serious, 1 patient) Chronic obstructive pulmonary disease (serious, 1 patient) Hypoxia (serious, 1 patient) Lung disorder (serious, 1 patient) Aspiration pneumonia (serious, 1 patient) Pulmonary embolism (serious, 3 patients) Respiratory failure (serious, 1 patient) Acute myeloid leukaemia (serious, 8 patients) Leukaemia (serious, 1 patient) Lung cancer metastatic (serious, 1 patient) Myelodysplastic syndrome (serious, 1 patient) Refractory anaemia with an excess of blasts (serious, 1 patient) Anxiety disorder (serious, 1 patient) Altered mood (serious, 1 patient) Atrial fibrillation (serious, 2 patients) Cardiac failure (serious, 2 patients) Diarrhoea (serious, 1 patient) Intussusception (serious, 1 patient) Tooth disorder (serious, 1 patient) Fall (serious, 1 patient) Injury (serious, 1 patient) Transfusion reaction (serious, 1 patient) Diabetes mellitus inadequate control (serious, 1 patient) Hyperglycaemia (serious, 1 patient) Hypoglycaemia (serious, 1 patient) Headache (serious, 1 patient) Renal failure (serious, 1 patient) Urinary incontinence (serious, 1 patient) Phlebitis (serious, 1 patient) Venous thrombosis (serious, 1 patient) Anaemia (serious, 4 patients) Febrile neutropenia (serious, 2 patients) Neutropenia (serious, 5 patients) Pancytopenia (serious, 1 patient) Thrombocytopenia (serious, 6 patients) International normalised ratio increased (serious, 1 patient) Urine human chorionic gonadotropin abnormal (serious, 1 patient) Fibromyalgia (serious, 1 patient) Muscle spasms (serious, 1 patient) Myalgia (serious, 1 patient) Pyoderma gangrenosum (serious, 1 patient) Cytogenetic abnormality (serious, 1 patient) Diarrhoea (below serious, 32 patients) Nausea (below serious, 16 patients) Constipation (below serious, 18 patients) Abdominal pain (below serious, 7 patients) Vomiting (below serious, 8 patients) Dry mouth (below serious, 4 patients) Abdominal pain upper (below serious, 8 patients) Dyspepsia (below serious, 4 patients) Flatulence (below serious, 2 patients) Fatigue (below serious, 17 patients) Oedema peripheral (below serious, 15 patients) Pyrexia (below serious, 11 patient) Non-cardiac chest pain (below serious, 5 patients) Influenza like illness (below serious, 5 patients) Oedema (below serious, 3 patients) Pain (below serious, 1 patient) Neutropenia (below serious, 55 patients) Anaemia (below serious, 10 patients) Leukopenia (below serious, 12 patients) Thrombocytopenia (below serious, 38 patients) Nasopharyngitis (below serious, 15 patients) Upper respiratory tract infection (below serious, 11 patient) Urinary tract infection (below serious, 6 patients) Bronchitis (below serious, 7 patients) Cystitis (below serious, 2 patients) Lower respiratory tract infection (below serious, 2 patients) Respiratory tract infection (below serious, 9 patients) Gastroenteritis (below serious, 7 patients) Gastroenteritis viral (below serious, 4 patients) Influenza (below serious, 5 patients) Oral herpes (below serious, 6 patients) Pharyngitis (below serious, 3 patients) Rhinitis (below serious, 4 patients) Headache (below serious, 12 patients) Dizziness (below serious, 8 patients) Paraesthesia (below serious, 8 patients) Peripheral sensory neuropathy (below serious, 4 patients) Muscle spasms (below serious, 12 patients) Back pain (below serious, 12 patients) Myalgia (below serious, 4 patients) Arthralgia (below serious, 6 patients) Pain in extremity (below serious, 5 patients) Musculoskeletal chest pain (below serious, 1 patient) Neck pain (below serious, 3 patients) Decreased appetite (below serious, 8 patients) Iron overload (below serious, 4 patients) Hypoalbuminaemia (below serious, 4 patients) Hypokalaemia (below serious, 7 patients) Hypomagnesaemia (below serious, 3 patients) Cough (below serious, 12 patients) Dyspnoea (below serious, 12 patients) Epistaxis (below serious, 3 patients) Dyspnoea exertional (below serious, 4 patients) Oropharyngeal pain (below serious, 7 patients) Pruritus (below serious, 16 patients) Dry skin (below serious, 10 patients) Rash (below serious, 18 patients) Hyperhidrosis (below serious, 2 patients) Petechiae (below serious, 3 patients) Insomnia (below serious, 6 patients) Depression (below serious, 4 patients) Anxiety (below serious, 3 patients) Contusion (below serious, 3 patients) Fall (below serious, 2 patients) Wound (below serious, 2 patients) Alanine aminotransferase increased (below serious, 7 patients) Weight decreased (below serious, 6 patients) Haematoma (below serious, 6 patients) Hypertension (below serious, 7 patients) Cataract (below serious, 1 patient) Vertigo (below serious, 8 patients) Musculoskeletal pain (below serious, 5 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00179621

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BSEP 402 BCRP 699 MRP2 383 OAT1 599 OAT3 642 OATP1B1 788 OATP1B3 706 OCT2 647 CYP 111 UGT1A1 204 CYP1A2 1524 CYP2C19 1478 CYP2E1 882	P-gp 1537 BCRP 561 MRP1 107 MRP2 205 MRP3 50 OAT1 326 OAT3 339 OATP1B1 406 OCT1 327 OCT2 355 MATE1 135 OCTN1 47 OCTN2 50	CYP 76 CYP1A 56 CYP2B 32 CYP2E 9 CYP3A 129 CYP4A 14

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 30.0	inconclusive
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
CYP 147	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
CYP 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
CYP1A 121	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no
CYP2B 40	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no
CYP2E 13	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no
CYP4A 33	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no	no (co-administration study) Comment: enzyme marker ethoxyresorufin O-dealkylase was used Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no	no (co-administration study) Comment: enzyme marker S-mephenytoin 4-hydroxylase Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no	no (co-administration study) Comment: enzyme marker tolbutamide methyl-hydroxylase Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no	no (co-administration study) Comment: enzyme marker bufuralol 1-hydroxylase Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no	no (co-administration study) Comment: enzyme marker lauric acid 11-hjydroxylase Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0	no	no (co-administration study) Comment: enzyme marker testosterone 6b-hydroxylase Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 27.0

Drug as victim

Target	Modality	Activity
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_BioPharmR.pdf Page: 30.0	inconclusive
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
MRP1 107	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
MRP3 50	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OCTN1 47	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no
OCTN2 50	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021880s057lbl.pdf Page: 30.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021880s000_Revlimid_PharmR.pdf Page: 5, 42

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63791	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63791
ChemicalBook	CB3855432	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3855432
MolPort	MolPort-003-848-370	https://www.molport.com/shop/molecule-link/MolPort-003-848-370
Selleck Chemicals	Lenalidomide	http://www.selleckchem.com/products/Lenalidomide.html
eMolecules	10609556	https://www.emolecules.com/cgi-bin/more?vid=10609556
eMolecules	32175817	https://www.emolecules.com/cgi-bin/more?vid=32175817

PubMed

Title	Date	PubMed
Circulating endothelial progenitor cells in multiple myeloma: implications and significance.	2005 Apr 15	15618473
Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma.	2005 Dec 15	16118317
Efficacy of lenalidomide in myelodysplastic syndromes.	2005 Feb 10	15703420
Immunomodulatory drugs (IMiDs) increase the production of IL-2 from stimulated T cells by increasing PKC-theta activation and enhancing the DNA-binding activity of AP-1 but not NF-kappaB, OCT-1, or NF-AT.	2005 Oct	16241859
Lenalidomide-induced warm autoimmune hemolytic anemia.	2006 Dec 10	17158529
Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis.	2006 Jul 1	16790586
Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications.	2006 Jul 15	16569772
Lenalidomide and venous thrombosis in multiple myeloma.	2006 May 11	16696148
A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma.	2006 Nov 15	16840727
Immunomodulatory drugs (IMiDs): a new treatment option for myelodysplastic syndromes.	2006 Oct	17076650
Lenalidomide: a new agent for patients with relapsed or refractory multiple myeloma.	2007 Aug	17723971
Risk of thrombosis with lenalidomide and its prevention with aspirin.	2007 Jan	17218586
Novel therapies in myeloma.	2007 Nov	17898564
Thromboembolic events with lenalidomide-based therapy for multiple myeloma.	2008 Apr 1	18278812
Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B.	2008 Feb	18217897
Azotemia associated with use of lenalidomide in plasma cell dyscrasias.	2008 Jun	18452093
Thrombosis of the corpora cavernosa complicating lenalidomide therapy of myelofibrosis.	2008 May	17870158
Diagnosis and the current trends in multiple myeloma therapy.	2008 Oct	19112817
Venous thromboembolism in myelodysplastic syndrome patients receiving lenalidomide: results from postmarketing surveillance and data mining techniques.	2009	19243209
Development of rapid light-chain deposition disease in hepatic arteries with severe ischemic cholangitis in a multiple myeloma patient treated with melphalan, prednisone and lenalidomide.	2009 Jan	19101782
Lenalidomide and rituximab in Waldenstrom's macroglobulinemia.	2009 Jan 1	19118065
A case of severe aplastic anemia secondary to treatment with lenalidomide for multiple myeloma.	2009 Mar	19018868
Lenalidomide-induced acute liver failure.	2009 Oct	20011646
Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis.	2009 Oct 1	19720904
Rapid control of previously untreated multiple myeloma with bortezomib-lenalidomide-dexamethasone (BLD).	2010 Apr	20423566
Successful treatment of MDS with lenalidomide, complicated by transient autoimmune hemolysis.	2010 Mar	19672596
Renal recovery with lenalidomide in a patient with bortezomib-resistant multiple myeloma.	2010 May	20351701
Activation of coagulation by lenalidomide-based regimens for the treatment of multiple myeloma.	2013	23696885

Patents

Sample Use Guides

In Vivo Use Guide

Multiple Myeloma: REVLIMID ([lenalidomide capsules) 25 mg once daily on Days 1-21 of repeated 28-day cycles. The recommended dose of dexamethasone is 40 mg once daily on Days 1-4, 9-12, and 17-20 of each 28-day cycle for the first 4 cycles of therapy and then 40 mg once daily orally on Days 1-4 every 28 days. Treatment is continued or modified based upon clinical and laboratory findings Myelodysplastic Syndromes: The recommended starting dose of REVLIMID is 10 mg daily Mantle Cell Lymphoma: The recommended starting dose of REVLIMID is 25 mg/day orally on Days 1-21 of repeated 28-day cycles for relapsed or refractory mantle cell lymphoma

Route of Administration: Oral

In Vitro Use Guide

Lenalidomide enhances signaling via CAR19 receptor. To determine the costimulatory effect of lenalidomide, CAR19 T cells were stimulated with immobilized anti-CD3 antibody (clone MEM-57) or, with immobilized anti-CAR serum (polyclonal goat anti-mouse IgG FAB2) in the presence (10 MM, 1 MM) or absence of lenalidomide. The production of IFN in to culture supernatant was determined with ELISA after overnight co-incubation

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:12:37 GMT 2023` Edited by `admin` on `Sat Dec 16 05:12:37 GMT 2023`
Record UNII	XQT0NAW8WD
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LENALIDOMIDE HEMIHYDRATE

Common Name

English

LENALIDOMIDE HYDRATE

Common Name

English

(±)-2,6-PIPERIDINEDIONE, 3-(4-AMINO-1,3-DIHYDRO-1-OXO-2H-ISOINDOL-2-YL)-, HYDRATE (2:1)

Systematic Name

English

LENALIDOMIDE HYDRATE [JAN]

Common Name

English

2,6-PIPERIDINEDIONE, 3-(4-AMINO-1,3-DIHYDRO-1-OXO-2H-ISOINDOL-2-YL)-, HYDRATE (2:1)

Systematic Name

English

Lenalidomide hemihydrate [WHO-DD]

Common Name

English

Code System Code Type Description

PUBCHEM

46220375