ALECTINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C30H34N4O2
Molecular Weight	482.6166
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1=C(C=C2C(=C1)C(=O)C3=C(NC4=C3C=CC(=C4)C#N)C2(C)C)N5CCC(CC5)N6CCOCC6

InChI

InChIKey=KDGFLJKFZUIJMX-UHFFFAOYSA-N

InChI=1S/C30H34N4O2/c1-4-20-16-23-24(17-26(20)34-9-7-21(8-10-34)33-11-13-36-14-12-33)30(2,3)29-27(28(23)35)22-6-5-19(18-31)15-25(22)32-29/h5-6,15-17,21,32H,4,7-14H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C30H34N4O2
Molecular Weight	482.6166
Charge	0
Count

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

Description
Sources: https://www.drugbank.ca/drugs/DB11363
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208434s000lbl.pdf

Alectinib is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. It was developed by Chugai Pharmaceutical Co. Japan, which is part of the Hoffmann-La Roche group. Alectinib is specifically used in the treatment of non-small cell lung cancer (NSCLC) expressing the ALK-EML4 (echinoderm microtubule-associated protein-like 4) fusion protein that causes proliferation of NSCLC cells. Inhibition of ALK prevents phosphorylation and subsequent downstream activation of STAT3 and AKT resulting in reduced tumour cell viability. Approved under accelerated approval in 2015, alectinib is indicated for use in patients who have progressed on or were not tolerant of crizotinib, which is associated with the development of resistance. Alectinib is marketed as Alecensa.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
ALK tyrosine kinase receptor 25 Target ID: CHEMBL4247 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208434s000lbl.pdf	Inhibitor 8297		1.9 nM [IC50]
SNU-2535 2 Target ID: SNU-2535 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26849637	Inhibitor 8297		33.1 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208434s000lbl.pdf	Primary		Approved 8429	Alecensa Approved Use ALECENSA is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. Launch Date 2015

C_max

Value	Dose	Analyte	Population
181 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ALECTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
665 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208434s003lbl.pdf	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ALECTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
255 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02838420	600 mg single, oral dose: 600 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
861 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02838420	600 mg 2 times / day steady, oral dose: 600 mg route of administration: oral experiment type: steady co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
107 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
85.5 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
306 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02838420	600 mg 2 times / day steady, oral dose: 600 mg route of administration: oral experiment type: steady co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:
71.4 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02838420	600 mg single, oral dose: 600 mg route of administration: oral experiment type: single co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:
17.5 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:
19.3 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:

AUC

Value	Dose	Analyte	Population
2790 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ALECTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
7430 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208434s003lbl.pdf	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ALECTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1590 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02838420	600 mg single, oral dose: 600 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
7760 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02838420	600 mg 2 times / day steady, oral dose: 600 mg route of administration: oral experiment type: steady co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
2820 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
3710 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
2920 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
3850 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
2890 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02838420	600 mg 2 times / day steady, oral dose: 600 mg route of administration: oral experiment type: steady co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:
471 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02838420	600 mg single, oral dose: 600 mg route of administration: oral experiment type: single co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:
465 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:
583 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:

T_1/2

Value	Dose	Analyte	Population
32 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	ALECTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
33 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208434s003lbl.pdf	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ALECTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
26.1 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
39.3 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
30.5 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:
24.5 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02621047	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	ALECTINIB METABOLITE M4 plasma	Homo sapiens population: unhealthy age: sex: food status:

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208434s003lbl.pdf	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ALECTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	unhealthy, 53 years n = 253 Health Status: unhealthy Condition: ALK-positive non-small cell lung cancer Age Group: 53 years Sex: M+F Population Size: 253 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	Other AEs: Cough... Other AEs: Cough (all grades, 19%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf
900 mg 2 times / day multiple, oral Highest studied dose Dose: 900 mg, 2 times / day Route: oral Route: multiple Dose: 900 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25153538	unhealthy, 56 years (range: 40–83 years) n = 6 Health Status: unhealthy Condition: locally advanced, or metastatic NSCLC Age Group: 56 years (range: 40–83 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/25153538	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/25153538
900 mg 2 times / day multiple, oral Highest studied dose Dose: 900 mg, 2 times / day Route: oral Route: multiple Dose: 900 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25153538/	unhealthy, 56 years (range: 40–83 years) n = 6 Health Status: unhealthy Condition: locally advanced, or metastatic NSCLC Age Group: 56 years (range: 40–83 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/25153538/	DLT: Headache... Dose limiting toxicities: Headache (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/25153538/
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	unhealthy, 56 years n = 134 Health Status: unhealthy Condition: ALK-positive NSCLC Age Group: 56 years Sex: M+F Population Size: 134 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	Other AEs: Hyperglycemia, Hyperglycemia... Other AEs: Hyperglycemia (all grades, 22%) Hyperglycemia (grade 3-4, 2.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	unhealthy, 56 years n = 143 Health Status: unhealthy Condition: ALK-positive NSCLC Age Group: 56 years Sex: M+F Population Size: 143 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	Other AEs: CPK increased, CPK increased... Other AEs: CPK increased (all grades, 37%) CPK increased (grade 3-4, 2.8%) Gamma-glutamyltransferase increased (all grades, 7%) Gamma-glutamyltransferase increased (grade 3-4, 0.7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	unhealthy, 56 years n = 146 Health Status: unhealthy Condition: ALK-positive NSCLC Age Group: 56 years Sex: M+F Population Size: 146 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	Other AEs: Hypoalbuminemia... Other AEs: Hypoalbuminemia (all grades, 14%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	unhealthy, 56 years n = 147 Health Status: unhealthy Condition: ALK-positive NSCLC Age Group: 56 years Sex: M+F Population Size: 147 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	Disc. AE: AST increased, ALT increased... Other AEs: AST increased, Alkaline phosphatase increased... AEs leading to discontinuation/dose reduction: AST increased (grade 3-4, 6%) ALT increased (grade 3-4, 6%) Other AEs: AST increased (all grades, 50%) Alkaline phosphatase increased (all grades, 50%) ALT increased (all grades, 40%) Creatinine increased (all grades, 38%) Creatinine increased (grade 3-4, 4.1%) Hypocalcemia (all grades, 29%) Hyponatremia (all grades, 18%) Hyponatremia (grade 3-4, 6%) Hypokalemia (all grades, 17%) Hypokalemia (grade 3-4, 2%) Anemia (all grades, 62%) Anemia (grade 3-4, 7%) Lymphopenia (all grades, 14%) Lymphopenia (grade 3-4, 1.4%) Neutropenia (all grades, 14%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	unhealthy, 56 years n = 152 Health Status: unhealthy Condition: ALK-positive NSCLC Age Group: 56 years Sex: M+F Population Size: 152 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	Disc. AE: Creatinine renal clearance decreased, Glomerular filtration rate decreased... Other AEs: Glomerular filtration rate decreased, Acute kidney injury... AEs leading to discontinuation/dose reduction: Creatinine renal clearance decreased (grade 3-4, 3.9%) Glomerular filtration rate decreased (grade 3-4, 3.9%) Acute kidney injury (grade 3-4, 3.9%) Pneumonia (3.3%) Hyperbilirubinemia (grade 3-4, 5%) Other AEs: Glomerular filtration rate decreased (all grades, 12%) Acute kidney injury (all grades, 12%) Constipation (all grades, 34%) Nausea (all grades, 14%) Nausea (grade 3-4, 0.7%) Diarrhea (all grades, 12%) Vomiting (all grades, 7%) Fatigue (all grades, 26%) Asthenia (all grades, 26%) Fatigue (grade 3-4, 1.3%) Asthenia (grade 3-4, 1.3%) Peripheral edema (all grades, 22%) Edema (all grades, 22%) Eyelid edema (all grades, 22%) Localized edema (all grades, 22%) Face edema (all grades, 22%) Peripheral edema (grade 3-4, 0.7%) Edema (grade 3-4, 0.7%) Eyelid edema (grade 3-4, 0.7%) Localized edema (grade 3-4, 0.7%) Face edema (grade 3-4, 0.7%) Myalgia (all grades, 23%) Musculoskeletal pain (all grades, 23%) Rash (all grades, 15%) Rash maculo-papular (all grades, 15%) Dermatitis acneiform (all grades, 15%) Erythema (all grades, 15%) Generalized rash (all grades, 15%) Rash macular (all grades, 15%) Rash papular (all grades, 15%) Exfoliative rash (all grades, 15%) Pruritic rash (all grades, 15%) Rash (grade 3-4, 0.7%) Rash maculo-papular (grade 3-4, 0.7%) Dermatitis acneiform (grade 3-4, 0.7%) Erythema (grade 3-4, 0.7%) Generalized rash (grade 3-4, 0.7%) Rash macular (grade 3-4, 0.7%) Rash papular (grade 3-4, 0.7%) Exfoliative rash (grade 3-4, 0.7%) Pruritic rash (grade 3-4, 0.7%) Dysgeusia (all grades, 3.3%) Hypogeusia (all grades, 3.3%) Dysgeusia (grade 3-4, 0.7%) Hypogeusia (grade 3-4, 0.7%) Blurred vision (all grades, 4.6%) Visual impairment (all grades, 4.6%) Vitreous floaters (all grades, 4.6%) Visual acuity reduced (all grades, 4.6%) Diplopia (all grades, 4.6%) Bradycardia (all grades, 11%) Sinus bradycardia (all grades, 11%) Blood creatinine increased (all grades, 12%) Creatinine renal clearance decreased (all grades, 12%) Blood creatinine increased (grade 3-4, 3.9%) Cardiac arrest (grade 5, 1 patient) Pneumonia (grade 5, 1 patient) Hyperbilirubinemia (all grades, 54%) Hyperkalemia (all grades, 12%) Hyperkalemia (grade 3-4, 1.4%) Hypophosphatemia (all grades, 9%) Hypophosphatemia (grade 3-4, 1.4%) Weight gain (9.9%) Photosensitivity reaction (5.3%) Stomatitis (3.3%) Interstitial lung disease (1.3%) Drug-induced liver injury (1.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	unhealthy, 56 years n = 253 Health Status: unhealthy Condition: ALK-positive non-small cell lung cancer Age Group: 56 years Sex: M+F Population Size: 253 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf	Other AEs: Headache, Headache... Other AEs: Headache (all grades, 17%) Headache (grade 3-4, 0.8%) Dyspnea (all grades, 16%) Dyspnea (grade 3-4, 3.17%) Dyspnea (grade 5, 1 patient) Back pain (all grades, 12%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP2C8 911 BCRP 699 P-gp 1461 BSEP 402 Cav1.2 45 CYP1A2 1524 CYP2B6 810 MRP2 383 OATP1B1 788 OAT1 599 OAT2 145 OCT2 647	OATP1B1 406 OATP1B3 350 BCRP 561 P-gp 1537	CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	yes [IC50 0.1 uM]
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	yes [IC50 0.9 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	yes [IC50 1.1 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=33 Page: -	yes [IC50 >10 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=33 Page: -	yes [IC50 >10 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=33 Page: -	yes [IC50 >10 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=33 Page: -	yes [IC50 >10 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=33 Page: -	yes [IC50 >10 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	yes [Ki 2 uM]	unlikely (co-administration study) Comment: Alectinib inhibits CYP2C8 in vitro, but simulations suggest that no clinically meaningful changes in repaglinide exposure would occur when it is coadministered with multiple doses of alectinib. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	yes
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	yes
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=34 Page: -	yes
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=34 Page: -	yes
OAT2 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=34 Page: -	yes
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=34 Page: -	yes
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=34 Page: -	yes
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	yes	no (co-administration study) Comment: No dose adjustment is recommended for concomitant CYP3A4 substrates, because no clinically meaningful changes in midazolam exposure were observed when alectinib at a dose of 600 mg twice daily was coadministered with a single midazolam dose Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	major	yes (co-administration study) Comment: Multiple dose of posaconazole increased the AUCinf of the combined exposure of alectinib and M4 by 1.4-fold when it was coadministered with a single 300 mg dose of alectinib. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=34 Page: -	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=8 Page: -	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000ClinPharmR.pdf#page=34 Page: -	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 49	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000PharmR.pdf#page=145 Page: -
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208434Orig1s000PharmR.pdf#page=145 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:90936	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:90936
ChemicalBook	CB62534680	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62534680
MolPort	MolPort-023-293-545	https://www.molport.com/shop/molecule-link/MolPort-023-293-545
Selleck Chemicals	ch5424802	http://www.selleckchem.com/products/ch5424802.html
ZINC	ZINC000066166864	http://zinc15.docking.org/substances/ZINC000066166864

PubMed

Title	Date	PubMed
		252160538
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.	2007 Aug 2	17625570
KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer.	2009 May 1	19383809
CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant.	2011 May 17	21575866
Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib.	2014 Nov 15	25228534
Perfect ALKemy: optimizing the use of ALK-directed therapies in lung cancer.	2014 Nov 15	25228532
Selective ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistance.	2014 Sep 1	24887559

Patents

Sample Use Guides

In Vivo Use Guide

600 mg orally twice daily. Administer with food.

Route of Administration: Oral

In Vitro Use Guide

Alectinib exhibited antiproliferative activity against SNU-2535 cells in vitro with IC50 of 33.1 nM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:32:16 GMT 2023` Edited by `admin` on `Sat Dec 16 05:32:16 GMT 2023`
Record UNII	LIJ4CT1Z3Y
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ALECTINIB

Official Name

English

ALECTINIB [MI]

Common Name

English

alectinib [INN]

Common Name

English

AF-802

Code

English

RO-5424802

Code

English

9-Ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

Systematic Name

English

ALECTINIB [USAN]

Common Name

English

CH5424802

Code

English

AF802

Code

English

RO5424802

Code

English

Alectinib [WHO-DD]

Common Name

English

5H-BENZO(B)CARBAZOLE-3-CARBONITRILE, 9-ETHYL-6,11-DIHYDRO-6,6-DIMETHYL-8-(4-(4-MORPHOLINYL)-1-PIPERIDINYL)-11-OXO-

Systematic Name

English

CH-5424802

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

462814