Catequentinib

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H22FN3O3
Molecular Weight	407.4375
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(OC3=C(F)C4=C(NC(C)=C4)C=C3)C=CN=C2C=C1OCC5(N)CC5

InChI

InChIKey=KSMZEXLVHXZPEF-UHFFFAOYSA-N

InChI=1S/C23H22FN3O3/c1-13-9-15-16(27-13)3-4-19(22(15)24)30-18-5-8-26-17-11-21(20(28-2)10-14(17)18)29-12-23(25)6-7-23/h3-5,8-11,27H,6-7,12,25H2,1-2H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28953502 | https://www.ncbi.nlm.nih.gov/pubmed/27716285 | https://clinicaltrials.gov/ct2/show/NCT01924195

AL3818 (anlotinib) is a receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFR1, VEGFR2/KDR, and VEGFR3), stem cell factor receptor (C-kit), platelet-derived growth factor (PDGFβ), and fibroblast growth factor receptors (FGFR1, FGFR2, and FGFR3). Anlotibib is a kind of innovative medicines approved by State Food and Drug Administration（SFDA:2011L00661) which was researched by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd. Phase III development is underway for the treatment of thyroid cancer, gastric cancer, leiomyosarcoma; non-small cell lung cancer; synovial sarcoma; thyroid cancer etc.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28953502 \| https://www.ncbi.nlm.nih.gov/pubmed/27716285 \| https://www.clinicaltrials.gov/ct2/show/NCT01924195	Antagonist 2849
Vascular endothelial growth factor receptor 2 112 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28953502 \| https://www.ncbi.nlm.nih.gov/pubmed/27716285 \| https://www.clinicaltrials.gov/ct2/show/NCT01924195 \| http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=9601	Antagonist 2849	0.2 nM [IC50]
Vascular endothelial growth factor receptor 3 41 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28953502 \| https://www.ncbi.nlm.nih.gov/pubmed/27716285 \| https://www.clinicaltrials.gov/ct2/show/NCT01924195 \| https://sage.airexmarket.com/documents/57f1b296b9ede0664300000b	Antagonist 2849	1.0 nM [IC50]
Stem cell growth factor receptor 57 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28953502 \| https://www.ncbi.nlm.nih.gov/pubmed/27716285 \| https://www.clinicaltrials.gov/ct2/show/NCT01924195 \|	Antagonist 2849
Fibroblast growth factor receptor 1 46 Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27716285 \| http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=9601	Antagonist 2849	7.7 null [pIC50]
Fibroblast growth factor receptor 2 25 Target ID: CHEMBL4142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27716285	Antagonist 2849

Conditions

Condition	Modality	Highest Phase	Product
Alveolar soft part sarcoma 2 Sources: https://clinicaltrials.gov/ct2/show/NCT03016819 http://adisinsight.springer.com/drugs/800038084	Primary	Phase III 665	Unknown Approved Use Unknown
Leiomyosarcoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT03016819 http://adisinsight.springer.com/drugs/800038084	Primary	Phase III 665	Unknown Approved Use Unknown
Synovial sarcoma 7 Sources: https://clinicaltrials.gov/ct2/show/NCT03016819 http://adisinsight.springer.com/drugs/800038084	Primary	Phase III 665	Unknown Approved Use Unknown
Soft tissue sarcoma 10 Sources: https://clinicaltrials.gov/ct2/show/NCT03016819 http://adisinsight.springer.com/drugs/800038084	Primary	Phase III 665	Unknown Approved Use Unknown
Medullary thyroid carcinoma 5 Sources: https://clinicaltrials.gov/ct2/show/NCT02586350	Primary	Phase III 665	Unknown Approved Use Unknown
Gastric cancer 53 Sources: https://clinicaltrials.gov/ct2/show/NCT02461407	Primary	Phase III 665	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: https://clinicaltrials.gov/ct2/show/NCT02388919	Primary	Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
5.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
687 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
562 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1066 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1585 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
102 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
95 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
116 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
98 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27716285/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:	ANLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
7.9% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29620050/			ANLOTINIB plasma	Homo sapiens

Doses

Dose	Population	Adverse events
12 mg 1 times / day multiple, oral Studied dose Dose: 12 mg, 1 times / day Route: oral Route: multiple Dose: 12 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30666799/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30666799/	Other AEs: Hemoptysis, Pneumonia... Other AEs: Hemoptysis (7 patients) Pneumonia (3 patients) Venous thromboembolism (3 patients) Interstitial lung disease (2 patients) Pneumothorax (2 patients) Proteinuria (2 patients) Respiratory failure (2 patients) Hypertension (1 pt) Abdominal pain (1 pt) Gastrointestinal hemorrhage (1 pt) Hypophosphatemia (1 pt) Oral mucositis (1 pt) Fatigue (1 pt) Hand foot syndrome (1 pt) Low density lipoprotein increased (1 pt) Appendicitis (1 pt) Hand-foot syndrome (7 patients) Hypertension (3 patients) Hypertriglyceridemia (2 patients) Diarrhea (1 pt) Liver dysfunction (1 pt) Anorexia (2 patients) Oral mucositis (2 patients) Arrhythmia (2 patients) Fatigue (1 pt) Dyspnea (1 pt) Hypertension (all grades, 67.7%) Fatigue (all grades, 52%) Anorexia (all grades, 45.9%) Hypertriglyceridemia (all grades, 44.6%) Hand-foot syndrome (all grades, 43.9%) Hypercholesteremia (all grades, 41.8%) Cough (all grades, 41.5%) Diarrhea (all grades, 35.4%) Low density lipoprotein increased (all grades, 31.3%) Proteinuria (all grades, 28.9%) Pharyngalgia (all grades, 28.2%) Blood bilirubin increased (all grades, 26.2%) Hyponatremia (all grades, 23.5%) Weight loss (all grades, 23.1%) Mucositis oral (all grades, 23.1%) Dysphonia (all grades, 23.1%) Low density lipoprotein increased (all grades, 21.1%) Hemoptysis (all grades, 20.4%) Hematuria (all grades, 15%) Upper respiratory infection (all grades, 12.6%) Urinary tract infection (all grades, 11.6%) Headache (all grades, 11.2%) Decreased platelet count (all grades, 10.5%) Hypertension (grade 3-4, 13.6%) Fatigue (grade 3-4, 1 pt) Anorexia (grade 3-4, 3 patients) Hypertriglyceridemia (grade 3-4, 9 patients) Hand-foot syndrome (grade 3-4, 11 patient) Cough (grade 3-4, 3 patients) Diarrhea (grade 3-4, 3 patients) GGT increased (grade 3-4, 16 patients) Proteinuria (grade 3-4, 7 patients) Pharyngalgia (grade 3-4, 2 patients) Pharyngalgia (grade 3-4, 5 patients) Hyponatremia (grade 3-4, 24 patients) Mucositis oral (grade 3-4, 3 patients) Dysphonia (grade 3-4, 3 patients) GGT elevation (grade 3-4, 2 patients) Hemoptysis (grade 3-4, 9 patients) Decreased platelet count (grade 3-4, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/30666799/
12 mg 1 times / day multiple, oral Studied dose Dose: 12 mg, 1 times / day Route: oral Route: multiple Dose: 12 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33586360/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/33586360/	Other AEs: Fatigue, Hypertension... Other AEs: Fatigue (all grades, 57%) Hypertension (all grades, 54%) Decreased appetite (all grades, 43%) Hypothyroidism (all grades, 36%) Palmar-plantar erythrodysesthesia (all grades, 27%) Proteinuria (all grades, 26%) Weight loss (all grades, 19%) Diarrhea (all grades, 17%) Leukopenia (all grades, 17%) Aspartate aminotransferase increased (all grades, 17%) Hypercholesterolemia (all grades, 15%) Hypertriglyceridemia (all grades, 14%) Gamma-glutamyltransferase increased (all grades, 14%) Alanine aminotransferase increased (all grades, 14%) Dysphonia (all grades, 14%) Low density lipoprotein increased (all grades, 13%) Lymphocytopenia (all grades, 13%) Oropharyngeal pain (all grades, 12%) Abdominal pain (all grades, 12%) Globulin urine present (all grades, 11%) Neutrophil count decreased (all grades, 11%) Rash (all grades, 10%) Nausea (all grades, 10%) Hyperglycemia (all grades, 5%) Insomnia (all grades, 1 pt) Fatigue (grade 3, 2%) Hypertension (grade 3, 16%) Decreased appetite (grade 3, 6%) Hypothyroidism (grade 3, 1 pt) Palmar-plantar erythrodysesthesia (grade 3, 2 patients) Proteinuria (grade 3, 1 pt) Electrocardiogram QTc interval prolonged (grade 3, 1 pt) Weight loss (grade 3, 3 patients) Electrocardiogram QTc interval prolonged (grade 3, 2 patients) Gamma-glutamyltransferase increased (grade 3, 3 patients) Alanine aminotransferase increased (grade 3, 1 pt) Increased low density lipoprotein (grade 3, 1 pt) Lymphocytopenia (grade 3, 2 patients) Oropharyngeal pain (grade 4, 1 pt) death (grade 5, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/33586360/

AEs

PubMed

Title	Date	PubMed
Endometrial Cancers Harboring Mutated Fibroblast Growth Factor Receptor 2 Protein Are Successfully Treated With a New Small Tyrosine Kinase Inhibitor in an Orthotopic Mouse Model.	2018-01	28953502
Safety and Efficacy of the S-1/Temozolomide Regimen in Patients with Metastatic Neuroendocrine Tumors.	2018	28817826
Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors.	2016-10-04	27716285

Patents

Sample Use Guides

In Vivo Use Guide

Anlotinib (AL3818) 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment)

Route of Administration: Oral

In Vitro Use Guide

AN3CA cells appeared the most sensitive to AL3818 with an IC50 value of 84 nM. The other cell lines were approximately 28- to 550-fold less sensitive to AL3818. HEC1B had an IC50 value of 46 uM, and MFE296 cells were sensitive to AL3818, with an IC50 value of 2.9 uM compared with 3.2, 28.9, 29, and 40 uM for Ishikawa, MFE280, KLE, and HEC1A, respectively.

Name

Type

Language

ANLOTINIB

Preferred Name

English

Catequentinib

Official Name

English

CATEQUENTINIB [USAN]

Common Name

English

1-[({4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinolin-7-yl}oxy)methyl]cyclopropan-1-amine

Systematic Name

English

Catequentinib [WHO-DD]

Common Name

English

ALTN

Common Name

English

AL3818

Code

English

AL-3818

Code

English

catequentinib [INN]

Common Name

English

Cyclopropanamine, 1-[[[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-quinolinyl]oxy]methyl]-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825