Page last updated: 2024-11-13

hmpl-013

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

HMPL-013: a VEGF receptor antagonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID Source	ID
PubMed CID	44480399
CHEMBL ID	4303214
SCHEMBL ID	947183
MeSH ID	M000598336

Synonyms (45)

Synonym
S5667
6-((6,7-dimethoxyquinazolin-4-yl)oxy)-n,2-dimethylbenzofuran-3-carboxamide
hmpl 013
BALLNEJQLSTPIO-UHFFFAOYSA-N
6-(6,7-dimethoxyquinazolin-4-yloxy)-n,2-dimethylbenzofuran-3-carboxamide
SCHEMBL947183
hmpl013
fruquintinib [inn]
elunate
gtpl9428
fruquintinib [usan:who-dd]
unii-49dxg3m5zw
fruquintinib [who-dd]
3-benzofurancarboxamide, 6-((6,7-dimethoxy-4-quinazolinyl)oxy)-n,2-dimethyl-
fruquintinib ,
who 10348
49dxg3m5zw ,
1194506-26-7
6-(6,7-dimethoxyquinazolin-4-yl)oxy-n,2-dimethyl-1-benzofuran-3-carboxamide
hmpl-013
fruquintinib [usan]
HY-19912
CS-5558
AKOS026750586
6-[(6,7-dimethoxyquinazolin-4-yl)oxy]-n,2-dimethyl-1-benzofuran-3-carboxamide
AS-73141
fruquintinib (hmpl-013)
DB11679
BCP15692
hmpl-013;hmpl013;hmpl 013
fruquintinib; hmpl-013
EX-A2262
6-[(6,7-dimethoxy-4-quinazolinyl)oxy]-n,2-dimethyl-3-benzofurancarboxamide
SB17123
CCG-268573
CHEMBL4303214
NCGC00481603-01
Q27259271
nsc-829498
nsc829498
C71641
B2693-470819
A898991
nsc801000
nsc-801000

Research Excerpts

Toxicity

Excerpt	Reference	Relevance
" Adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v4."	( A Phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors. Cao, J; Chen, Z; Fan, S; Li, J; Li, K; Peng, W; Su, W; Zhang, J, 2016)	0.43
" The most common grade 3/4 adverse events were hand-foot skin reaction, hypertension, and thrombocytopenia."	( A Phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors. Cao, J; Chen, Z; Fan, S; Li, J; Li, K; Peng, W; Su, W; Zhang, J, 2016)	0.43
" The most common grade 3-4 adverse events were hypertension and hand-foot skin reaction."	( Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study. Bai, Y; Cao, J; Fan, S; Hua, Y; Li, J; Liu, T; Pan, H; Shen, L; Su, W; Wang, L; Xu, J; Xu, RH; Zhang, D, 2017)	0.46
" However, its safety profile, including adverse events of special interest (AESIs) and treatment-emergent adverse events (TEAEs) by age, sex, and body mass index (BMI), is not well known."	( Safety Profile and Adverse Events of Special Interest for Fruquintinib in Chinese Patients with Previously Treated Metastatic Colorectal Cancer: Analysis of the Phase 3 FRESCO Trial. Bai, Y; Cao, P; Chen, D; Chen, H; Chen, Z; Cheng, Y; Deng, Y; Fan, S; Guo, W; Guo, X; Han, R; Li, J; Li, W; Liu, T; Ma, D; Pan, H; Qin, S; Shen, L; Shu, Y; Sun, S; Wang, H; Wang, N; Wang, S; Wu, C; Xu, J; Xu, N; Xu, R; Yang, L; Yu, Z; Yuan, Y; Zhang, B; Zhong, H; Zhou, J, 2020)	0.56
" The FRESCO-2 study is being conducted globally to determine how safe and effective fruquintinib is at treating patients with metastatic colorectal cancer that has grown or spread following other forms of treatment, such as chemotherapy."	( FRESCO-2: a global Phase III study investigating the efficacy and safety of fruquintinib in metastatic colorectal cancer. Chien, C; Dasari, A; Eng, C; Kania, M; Schelman, W; Sobrero, A; Tabernero, J; Yang, Z; Yao, J; Yoshino, T, 2021)	0.62
" The main adverse events (AEs) included reactive cutaneous capillary endothelial proliferation (RCCEP) (81."	( Efficacy and safety of regorafenib or fruquintinib plus camrelizumab in patients with microsatellite stable and/or proficient mismatch repair metastatic colorectal cancer: an observational pilot study. Jiang, FE; Liu, AN; Yu, CY; Zhang, HJ, 2021)	0.62
" The primary outcome was time-to-treatment failure (TTF), and secondary outcomes were overall survival (OS) and adverse events."	( Efficacy and Safety Comparison of Regorafenib and Fruquintinib in Metastatic Colorectal Cancer-An Observational Cohort Study in the Real World. Cao, Y; Chen, M; Li, J; Lu, M; Peng, Z; Qi, C; Shen, L; Wang, X; Wang, Z; Zhang, J; Zhang, Q, 2022)	0.72
" The incidences of most adverse events were similar between the two groups, while any grade of hand-foot skin reaction and hyperbilirubinemia were more frequently observed in the regorafenib group and ≥grade 3 hypertension was more common in the fruquintinib group."	( Efficacy and Safety Comparison of Regorafenib and Fruquintinib in Metastatic Colorectal Cancer-An Observational Cohort Study in the Real World. Cao, Y; Chen, M; Li, J; Lu, M; Peng, Z; Qi, C; Shen, L; Wang, X; Wang, Z; Zhang, J; Zhang, Q, 2022)	0.72
" The DCR, progression-free survival (PFS), and adverse reactions of the drug were recorded and reviewed."	( Efficacy and safety of fruquintinib as third- or further-line therapy for patients with advanced bone and soft tissue sarcoma: a multicenter retrospective study. Ding, X; Hu, H; Li, Q; Liang, J; Liu, Y; Zhang, Y; Zhou, Y, 2023)	0.91

Pharmacokinetics

Excerpt	Reference	Relevance
" It shows moderate oral bioavailability of 42-53 % and Tmax < 4 h in mouse, rat, dog and monkey, with exposure-dose linearity proved in rats and dogs."	( Preclinical pharmacokinetics and disposition of a novel selective VEGFR inhibitor fruquintinib (HMPL-013) and the prediction of its human pharmacokinetics. Gu, Y; Guo, L; Li, K; Ren, H; Sai, Y; Su, W; Wang, J; Zhang, L; Zhang, W, 2014)	0.62
" Pharmacokinetic parameters were measured after a single dose and in multiple dosing."	( A Phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors. Cao, J; Chen, Z; Fan, S; Li, J; Li, K; Peng, W; Su, W; Zhang, J, 2016)	0.43
" PK analysis showed good and rapid absorption followed by slow terminal elimination with a mean half-life of approximately 42 h which was consistent across all dose groups."	( A Phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1, -2, and -3 tyrosine kinases in Chinese patients with advanced solid tumors. Cao, J; Chen, Z; Fan, S; Li, J; Li, K; Peng, W; Su, W; Zhang, J, 2016)	0.43
" The objective of the study was to investigate the tolerability and effect of high-fat food on the pharmacokinetic profile of a fruquintinib capsule in healthy Chinese subjects."	( Effects of a High-fat Meal on the Pharmacokinetics of the VEGFR Inhibitor Fruquintinib: A Randomized Phase I Study in Healthy Subjects. Chen, Q; Fan, S; Jia, J; Li, K; Li, T; Liu, Y; Qian, H; Sai, Y; Su, W; Wang, W; Yu, C, 2019)	0.51
" Blood samples for pharmacokinetic analysis were collected at the designated time points."	( Effects of a High-fat Meal on the Pharmacokinetics of the VEGFR Inhibitor Fruquintinib: A Randomized Phase I Study in Healthy Subjects. Chen, Q; Fan, S; Jia, J; Li, K; Li, T; Liu, Y; Qian, H; Sai, Y; Su, W; Wang, W; Yu, C, 2019)	0.51
" The analytical method had been validated and applied to a pharmacokinetic study of fruquintinib in rat."	( Validated UPLC-MS/MS method for quantification of fruquintinib in rat plasma and its application to pharmacokinetic study. Guo, J; Luo, SB; Mei, YB; Qiu, XJ; Xie, SL; Ye, LY; Zhang, Q, 2019)	0.51

Bioavailability

Excerpt	Reference	Relevance
" It shows moderate oral bioavailability of 42-53 % and Tmax < 4 h in mouse, rat, dog and monkey, with exposure-dose linearity proved in rats and dogs."	( Preclinical pharmacokinetics and disposition of a novel selective VEGFR inhibitor fruquintinib (HMPL-013) and the prediction of its human pharmacokinetics. Gu, Y; Guo, L; Li, K; Ren, H; Sai, Y; Su, W; Wang, J; Zhang, L; Zhang, W, 2014)	0.62
"The overall bioavailability of the evaluated formulation of fruquintinib was not affected by the consumption of a high-fat, high-calorie meal prior to dosing."	( Effects of a High-fat Meal on the Pharmacokinetics of the VEGFR Inhibitor Fruquintinib: A Randomized Phase I Study in Healthy Subjects. Chen, Q; Fan, S; Jia, J; Li, K; Li, T; Liu, Y; Qian, H; Sai, Y; Su, W; Wang, W; Yu, C, 2019)	0.51
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."	( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)	0.51

Dosage Studied

Excerpt	Relevance	Reference
" It would require high potency (low effective drug concentrations) and sufficient drug exposures at tolerated doses so that the drug concentration can be maintained above effective drug concentration for target inhibition within the dosing period."	( Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cai, H; Cui, Y; Gu, Y; Guo, M; Hong, M; Liang, J; Long, J; Ni, L; Qing, W; Ren, Y; Sai, Y; Su, W; Sun, J; Sun, Q; Yang, H; Yang, Z; Yin, F; Zhang, M; Zhang, W; Zhang, Z; Zhou, F; Zhou, J, 2014)	0.4
" Steady-state was achieved after 14 days of QD dosing with systemic exposure four-fold higher than that after a single dose."	( Phase 1/1b open-label, dose-escalation study of fruquintinib in patients with advanced solid tumors in the United States. Chien, C; Gonzalez, M; Kania, M; Schelman, W; Ukrainskyj, S; Wang-Gillam, A; Yang, Z; Yeckes-Rodin, H, 2023)	0.91

[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (6)

Assay ID	Title	Year	Journal	Article
AID1346987	P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347411	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1346986	P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1345548	Human fms related tyrosine kinase 1 (Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family)	2014	Cancer biology & therapy, , Volume: 15, Issue:12	Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy.
AID1345520	Human fms related tyrosine kinase 4 (Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family)	2014	Cancer biology & therapy, , Volume: 15, Issue:12	Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy.
AID1345506	Human kinase insert domain receptor (Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family)	2014	Cancer biology & therapy, , Volume: 15, Issue:12	Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (43)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	17 (39.53)	24.3611
2020's	26 (60.47)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 18.26

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

Metric	This Compound (vs All)
Research Demand Index	18.26 (24.57)
Research Supply Index	4.06 (2.92)
Research Growth Index	4.69 (4.65)
Search Engine Demand Index	15.26 (26.88)
Search Engine Supply Index	2.00 (0.95)

This Compound (18.26)

All Compounds (24.57)

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	13 (29.55%)	5.53%
Reviews	8 (18.18%)	6.00%
Case Studies	2 (4.55%)	4.05%
Observational	2 (4.55%)	0.25%
Other	19 (43.18%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
thymine [no description available]	4.24	2	0	pyrimidine nucleobase; pyrimidone	Escherichia coli metabolite; human metabolite; mouse metabolite
uracil 2,4-dihydroxypyrimidine: a urinary biomarker for bipolar disorder	4.24	2	0	pyrimidine nucleobase; pyrimidone	allergen; Daphnia magna metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; prodrug; Saccharomyces cerevisiae metabolite
trifluridine Trifluridine: An antiviral derivative of THYMIDINE used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to HERPES SIMPLEX virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557). trifluridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-trifluoromethyluracil as the nucleobase. An antiviral drug used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis.	6.25	4	1	nucleoside analogue; organofluorine compound; pyrimidine 2'-deoxyribonucleoside	antimetabolite; antineoplastic agent; antiviral drug; EC 2.1.1.45 (thymidylate synthase) inhibitor
pyrroles 1H-pyrrole : A tautomer of pyrrole that has the double bonds at positions 2 and 4.. pyrrole : A five-membered monocyclic heteroarene comprising one NH and four CH units which forms the parent compound of the pyrrole group of compounds. Its five-membered ring structure has three tautomers. A 'closed class'.. azole : Any monocyclic heteroarene consisting of a five-membered ring containing nitrogen. Azoles can also contain one or more other non-carbon atoms, such as nitrogen, sulfur or oxygen.	3.23	1	0	pyrrole; secondary amine
quinazolines Quinazolines: A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.. quinazoline : A mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.. quinazolines : Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives.	15.47	43	18	azaarene; mancude organic heterobicyclic parent; ortho-fused heteroarene; quinazolines
paclitaxel Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).	2.6	1	0	taxane diterpenoid; tetracyclic diterpenoid	antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent
benzofurans Benzofurans: Compounds that contain a BENZENE ring fused to a furan ring.	15.74	45	19
ma-1 tipiracil: inhibits thymidine phosphorylase. tipiracil : A member of the class of pyrimidones that is uracil substituted by chloro and (2-iminopyrrolidin-1-yl)methyl groups at positions 5 and 6 respectively. Used (as the hydrochloride salt) in combination with trifluridine, a nucleoside metabolic inhibitor, for treatment of advanced/relapsed unresectable colorectal cancer.	2.6	1	0	carboxamidine; organochlorine compound; pyrimidone; pyrrolidines	antineoplastic agent; EC 2.4.2.4 (thymidine phosphorylase) inhibitor
regorafenib [no description available]	7	7	1	(trifluoromethyl)benzenes; aromatic ether; monochlorobenzenes; monofluorobenzenes; phenylureas; pyridinecarboxamide	antineoplastic agent; hepatotoxic agent; tyrosine kinase inhibitor
famitinib famitinib: structure in first source	3.23	1	0
icotinib [no description available]	3.23	1	0
ast 1306 AST 1306: an antineoplastic agent that inhibits epidermal growth factor receptors 1 and 2; structure in first source	3.23	1	0	quinazolines

Condition	Indicated	Relationship Strength	Studies	Trials
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	0	3.78	3	0
Cancer of Colon [description not available]	0	8.33	7	2
Colorectal Cancer [description not available]	0	16.46	49	29
Colonic Neoplasms Tumors or cancer of the COLON.	1	10.33	7	2
Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.	1	22.78	147	87
Cancer of Rectum [description not available]	0	7.76	5	2
Rectal Neoplasms Tumors or cancer of the RECTUM.	1	9.76	5	2
Benign Neoplasms [description not available]	0	8.15	6	5
Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	1	10.15	6	5
Cancer of Stomach [description not available]	0	2.6	1	0
Stomach Neoplasms Tumors or cancer of the STOMACH.	1	4.6	1	0
Cognitive Decline [description not available]	0	3.52	4	0
Acute Confusional Senile Dementia [description not available]	0	3.52	4	0
Amyloid Angiopathy, Cerebral [description not available]	0	3.52	4	0
Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)	0	3.52	4	0
Cerebral Amyloid Angiopathy A heterogeneous group of sporadic or familial disorders characterized by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES. Clinical features include multiple, small lobar CEREBRAL HEMORRHAGE; cerebral ischemia (BRAIN ISCHEMIA); and CEREBRAL INFARCTION. Cerebral amyloid angiopathy is unrelated to generalized AMYLOIDOSIS. Amyloidogenic peptides in this condition are nearly always the same ones found in ALZHEIMER DISEASE. (from Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005)	0	3.52	4	0
Cognitive Dysfunction Diminished or impaired mental and/or intellectual function.	0	3.52	4	0
Sarcoma, Epithelioid [description not available]	0	2.6	1	0
Sarcoma A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant.	1	4.6	1	0
Soft Tissue Neoplasms Neoplasms of whatever cell type or origin, occurring in the extraskeletal connective tissue framework of the body including the organs of locomotion and their various component structures, such as nerves, blood vessels, lymphatics, etc.	0	2.6	1	0
DDPAC [description not available]	0	2.6	1	0
Frontotemporal Dementia The most common clinical form of FRONTOTEMPORAL LOBAR DEGENERATION, this dementia presents with personality and behavioral changes often associated with disinhibition, apathy, and lack of insight.	0	2.6	1	0
Metastase [description not available]	0	4.72	5	0
Angiogenesis, Pathologic [description not available]	0	2.21	1	0
Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.	0	4.72	5	0
Disease Exacerbation [description not available]	0	3.17	1	0
Carcinoma, Non-Small Cell Lung [description not available]	0	9.47	6	2
Cancer of Lung [description not available]	0	9.47	6	2
Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.	1	11.47	6	2
Lung Neoplasms Tumors or cancer of the LUNG.	1	11.47	6	2
Microsatellite Instability The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.	0	2.25	1	0
Adenocarcinoma, Basal Cell [description not available]	0	10.78	10	9
Adenocarcinoma A malignant epithelial tumor with a glandular organization.	0	10.78	10	9
Choroid Neovascularization [description not available]	0	2.25	1	0

chemdatabank.com