ORANTINIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H18N2O3
Molecular Weight	310.3478
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cc1c(CCC(=O)O)c(C)[nH]c1/C(/[H])=C\2/c3ccccc3N=C2O

InChI

InChIKey=NHFDRBXTEDBWCZ-ZROIWOOFSA-N

InChI=1S/C18H18N2O3/c1-10-12(7-8-17(21)22)11(2)19-16(10)9-14-13-5-3-4-6-15(13)20-18(14)23/h3-6,9,19H,7-8H2,1-2H3,(H,20,23)(H,21,22)/b14-9-

HIDE SMILES / InChI

Molecular Formula	C18H18N2O3
Molecular Weight	310.3478
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11779084 | https://www.ncbi.nlm.nih.gov/pubmed/11892927 | https://www.healio.com/hematology-oncology/gastrointestinal-cancer/news/online/%7B98d87e56-a37b-462f-a7ac-17a361e432e3%7D/taiho-pharmaceutical-to-terminate-phase-3-trial-of-orantinib-tace-for-hepatocellular-carcinoma | https://www.ncbi.nlm.nih.gov/pubmed/10945623

Orantinib (SU-6668) is an orally bioavailable receptor tyrosine kinase inhibitor. Orantinib binds to and inhibits the autophosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR), thereby inhibiting angiogenesis and cell proliferation. Orantinib also inhibits the phosphorylation of the stem cell factor receptor tyrosine kinase c-kit, often expressed in acute myelogenous leukemia cells. Orantinib was in phase II clinical trials for the treatment of breast cancer. It was also in phase III clinical trials for the treatment of hepatocellular carcinoma. However, this research was terminated in 2014. The compound was originally developed by Sugen (subsidiary of Pfizer). In 1998, a co-development agreement took place between Sugen and Taiho for the compound.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Platelet-derived growth factor receptor beta 51 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10602697 \| https://www.ncbi.nlm.nih.gov/pubmed/10945623	Inhibitor 7728	0.06 µM [IC50]
Vascular endothelial growth factor receptor 2 95 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10602697 \| https://www.ncbi.nlm.nih.gov/pubmed/10945623	Antagonist 2575	2.43 µM [IC50]
Fibroblast growth factor receptor 1 44 Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10602697	Inhibitor 7728	3.04 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatocellular carcinoma 78 Sources: https://clinicaltrials.gov/ct2/show/NCT01465464 http://adisinsight.springer.com/drugs/800011006	Primary		Phase III 643	Unknown Approved Use Unknown
Solid tumors 140 Sources: http://adisinsight.springer.com/drugs/800011006 https://clinicaltrials.gov/ct2/show/NCT00024206 https://clinicaltrials.gov/ct2/show/NCT00024063	Primary		Phase I 409	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P002LDE	https://www.1pchem.com/search?query=1P002LDE
1PlusChem LLC	1P0037YL	https://www.1pchem.com/search?query=1P0037YL
AChemBlock	10389	http://www.achemblock.com/catalogsearch/result/?q=10389
AK Scientific	SYN1085	https://aksci.com/item_detail.php?cat=SYN1085
AK Scientific	X7490	https://aksci.com/item_detail.php?cat=X7490
Alfa Chemistry	99975	http://www.alfa-chemistry.com/search.aspx?q=99975
Alfa Chemistry	ACM210644625	http://www.alfa-chemistry.com/search.aspx?q=ACM210644625
Angene	AGN-PC-0R11YW	http://www.angenechemical.com/productshow/AGN-PC-0R11YW.html
AstaTech	32575	http://astatechinc.com/CPSResult.php?CRNO=32575
Axon MedChem	1891	https://www.axonmedchem.com/product/1891
BLD Pharm	BD226284	http://www.bldpharm.com/search/Search.html?keyword=BD226284
BioSynth	J-502593	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-502593
Cayman Chemical	13873	http://www.caymanchem.com/app/template/Product.vm/catalog/13873
Chem Scene	CS-0197	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0197
ChemShuttle	112411	https://www.chemshuttle.com/catalogsearch/result/?q=112411
Combi-Blocks	QJ-9930	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-9930
Excenen	EX-A471	http://www.excenen.com/searchresultlist.php?id=EX-A471
Exclusive Chemistry	2125	http://www.exchemistry.com/chem-catalog/product-2125.html
KeyOrganics	AS-16238	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16238
Lab Network	LN01301260	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01301260
Lab Network	LN02195818	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN02195818
Matrix Scientific	132613	http://www.matrixscientific.com/132613.html
MedChem Express	HY-10517	https://www.medchemexpress.com/search.html?q=HY-10517&ft=&fa=&fp=
MolPort	MolPort-002-345-646	https://www.molport.com/shop/molecule-link/MolPort-002-345-646
Molcore	MC110858	http://www.molcore.com/CatMC110858.html
Molcore	MC116202	http://www.molcore.com/CatMC116202.html
Molnova	M13746	https://www.molnova.com/en/serch-list.html?keywords=M13746
MuseChem	I002859	https://www.musechem.com/product/I002859.html
ShangHai Biochempartner	BCP000222	http://www.biochempartner.com/search_BCP000222
ShangHai Biochempartner	BCP01984	http://www.biochempartner.com/search_BCP01984
Tocris	3335	https://www.tocris.com/search.php?Type=QuickSearch&Value=3335
Toronto Research Chemicals	D457088	https://www.trc-canada.com/product-detail/?CatNum=D457088
Toronto Research Chemicals	T797550	https://www.trc-canada.com/product-detail/?CatNum=T797550
Wonderchem	WD05L8N	http://www.wonder-chem.com/search.html?text=WD05L8N
eMolecules	44842437	https://orderbb.emolecules.com/search/#?query=44842437
eMolecules	8774906	https://orderbb.emolecules.com/search/#?query=8774906
mcule	MCULE-6548478930	https://mcule.com/MCULE-6548478930/
mcule	MCULE-6952494198	https://mcule.com/MCULE-6952494198/

PubMed

Title	Date	PubMed
		252160544
Design, synthesis, and evaluations of substituted 3-[(3- or 4-carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-ones as inhibitors of VEGF, FGF, and PDGF receptor tyrosine kinases.	1999 Dec 16	10602697
In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model.	2004 Jan 15	14760097
Combined antiangiogenic and immune therapy of prostate cancer.	2005	16132614
Combined inhibition of vascular endothelial growth factor and platelet-derived growth factor signaling: effects on the angiogenesis, microcirculation, and growth of orthotopic malignant gliomas.	2005 Feb	15739567
Vascular endothelial growth factor: a therapeutic target for tumors of the Ewing's sarcoma family.	2005 Mar 15	15788688
Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU-68).	2005 Mar 20	15551349
Dose-finding study of the multitargeted tyrosine kinase inhibitor SU6668 in patients with advanced malignancies.	2005 Sep 1	16144927
Potent platelet-derived growth factor-beta receptor (PDGF-betaR) inhibitors: Synthesis and structure-activity relationships of 7-[3-(cyclohexylmethyl)ureido]-3-{1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}quinoxalin-2(1H)-one derivatives.	2007 Feb	17268099
5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases.	2009 Feb 1	19110422
Acenaphtho[1,2-b]pyrrole-based selective fibroblast growth factor receptors 1 (FGFR1) inhibitors: design, synthesis, and biological activity.	2011 Jun 9	21517068

Patents

Sample Use Guides

In Vivo Use Guide

Orantinib at 200 mg, twice per day, or placebo was given orally until TACE failure or unacceptable toxicity.

Route of Administration: Oral

In Vitro Use Guide

Orantinib (SU-6668) inhibited PDGF-stimulated PDGFRb tyrosine phosphorylation in NIH-3T3 cells overexpressing PDGFRb at a minimum concentration of 0.03–0.1 uM. SU-6668 inhibited acidic FGF-induced phosphorylation of the FGFR1 substrate 2 (FRS-2) at concentrations of 10 uM and higher. However, SU-6668 had no detectable effect on epidermal growth factor-stimulated EGFR tyrosine phosphorylation in NIH-3T3 cells overexpressing EGFR at concentrations of up to 100 uM. Orantinib (SU-6668) inhibited VEGF-driven mitogenesis of HUVECs in a dose-dependent manner with a mean IC50 of 0.34 uM.

Substance Class	Chemical Created by `admin` on `Sat Jun 26 07:26:18 UTC 2021` Edited by `admin` on `Sat Jun 26 07:26:18 UTC 2021`
Record UNII	9RL37ZZ665
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ORANTINIB

Official Name

English

1H-PYRROLE-3-PROPANOIC ACID, 5-((1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE)METHYL)-2,4-DIMETHYL-

Common Name

English

NSC-702827

Code

English

TSU-68

Code

English

5-((1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE)METHYL)-2,4-DIMETHYL-1H-PYRROLE-3-PROPANOIC ACID

Systematic Name

English

3-(2,4-DIMETHYL-5-(2-OXO-1,2-DIHYDROINDOL-3-YLIDENEMETHYL)-1H-PYRROL-3-YL)PROPIONIC ACID

Systematic Name

English

3-(2,4-DIMETHYL-5-(((3Z)-2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL)-1H-PYRROL-3-YL)PROPANOIC ACID

Systematic Name

English

3-(2,4-DIMETHYL-5-((2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL)-1H-PYRROL-3-YL)PROPIONIC ACID

Systematic Name

English

ORANTINIB [INN]

Common Name

English

3-(4-(2-CARBOXYETHYL)-3,5-DIMETHYLPYRROL-2-METHYLIDENYL)-2-INDOLINONE

Common Name

English

ORANTINIB [WHO-DD]

Common Name

English

SU-6668

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1967