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MedKoo Cat#: 206321 | Name: Orantinib
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Orantinib, also known as TSU-68；SU6668, 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. Check for active clinical trials or closed clinical trials using this agent.

Chemical Structure

Orantinib
Orantinib
CAS#252916-29-3

Theoretical Analysis

MedKoo Cat#: 206321

Name: Orantinib

CAS#: 252916-29-3

Chemical Formula: C18H18N2O3

Exact Mass: 310.1317

Molecular Weight: 310.35

Elemental Analysis: C, 69.66; H, 5.85; N, 9.03; O, 15.47

Price and Availability

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10mg USD 195.00
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Synonym
TSU68; TSU 68; TSU-68; SU6668; SU 6668; SU-6668; NSC 702827; Orantinib.
IUPAC/Chemical Name
(Z)-3-(2,4-dimethyl-5-((2-oxoindolin-3-ylidene)methyl)-1H-pyrrol-3-yl)propanoic aciD
InChi Key
NHFDRBXTEDBWCZ-ZROIWOOFSA-N
InChi Code
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-
SMILES Code
O=C(O)CCC1=C(C)NC(/C=C2C(NC3=C\2C=CC=C3)=O)=C1C
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
TSU68 is an inhibitor of vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor beta, and fibroblast growth factor receptor 1 (FGFR1).   TSU-68 (SU-6668) was developed as an inhibitor of RTKs involved in VEGF, bFGF and PDGF signaling, which then inhibits endothelial cell proliferation.  In a in vivo trial,  TSU-68 was administered orally at a dose of 200 mg/kg twice daily. Mice bearing human colon carcinoma, HT-29, or WiDr xenografts were treated for 16 days. As TSU-68 significantly inhibited tumor growth and liver metastasis formation of human colon cancer xenografts, probably through anti-angiogenic activity, this agent may be useful for the treatment of colon cancer. see. http://www.ncbi.nlm.nih.gov/pubmed/16077974.         
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Orantinib (SU6668; TSU-68) is a multi-targeted receptor tyrosine kinase inhibitor with Kis of 2.1 μM, 8 nM and 1.2 μM for Flt-1, PDGFRβ and FGFR1.
In vitro activity:
Biochemical kinetic studies using isolated Flk-1, FGF receptor 1, and PDGF receptor beta kinases revealed that SU6668 has competitive inhibitory properties with respect to ATP. Cocrystallographic studies of SU6668 in the catalytic domain of FGF receptor 1 substantiated the adenine mimetic properties of its oxindole core. Molecular modeling of SU6668 in the ATP binding pockets of the FIk-1/KDR and PDGF receptor kinases provided insight to explain the relative potency and selectivity of SU6668 for these receptors. In cellular systems, SU6668 inhibited receptor tyrosine phosphorylation and mitogenesis after stimulation of cells by appropriate ligands. Reference: Cancer Res. 2000 Aug 1;60(15):4152-60. https://pubmed.ncbi.nlm.nih.gov/10945623/
In vivo activity:
A s.c. tumor model of HT29 human colon carcinoma in athymic mice was used. DCE-MRI clearly detected the early effect (after 24 h of treatment) of SU6668 on tumor vasculature as a 51% and 26% decrease in the average vessel permeability measured in the tumor rim and core (respectively). SU6668 greatly inhibited tumor growth, with 60% inhibition at 14 days of treatment. Reference: Clin Cancer Res. 2004 Jan 15;10(2):739-50. https://pubmed.ncbi.nlm.nih.gov/14760097/
Solvent mg/mL mM
Solubility
DMF 5.0 16.11
DMF:PBS (pH 7.2) (1:1) 0.5 1.61
DMSO 48.9 157.51
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 310.35 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Hara Y, Yamashita T, Oishi N, Nio K, Hayashi T, Nomura Y, Yoshida M, Hayashi T, Hashiba T, Asahina Y, Kondo M, Okada H, Sunagozaka H, Honda M, Kaneko S. TSU-68 ameliorates hepatocellular carcinoma growth by inhibiting microenvironmental platelet-derived growth factor signaling. Anticancer Res. 2015 Mar;35(3):1423-31. PMID: 25750293. 2. Laird AD, Vajkoczy P, Shawver LK, Thurnher A, Liang C, Mohammadi M, Schlessinger J, Ullrich A, Hubbard SR, Blake RA, Fong TA, Strawn LM, Sun L, Tang C, Hawtin R, Tang F, Shenoy N, Hirth KP, McMahon G, Cherrington. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res. 2000 Aug 1;60(15):4152-60. PMID: 10945623. 3. Yamamoto M, Kikuchi H, Ohta M, Kawabata T, Hiramatsu Y, Kondo K, Baba M, Kamiya K, Tanaka T, Kitagawa M, Konno H. TSU68 prevents liver metastasis of colon cancer xenografts by modulating the premetastatic niche. Cancer Res. 2008 Dec 1;68(23):9754-62. doi: 10.1158/0008-5472.CAN-08-1748. PMID: 19047154. 4. Marzola P, Degrassi A, Calderan L, Farace P, Crescimanno C, Nicolato E, Giusti A, Pesenti E, Terron A, Sbarbati A, Abrams T, Murray L, Osculati F. In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model. Clin Cancer Res. 2004 Jan 15;10(2):739-50. doi: 10.1158/1078-0432.ccr-0828-03. PMID: 14760097.
In vitro protocol:
1. Hara Y, Yamashita T, Oishi N, Nio K, Hayashi T, Nomura Y, Yoshida M, Hayashi T, Hashiba T, Asahina Y, Kondo M, Okada H, Sunagozaka H, Honda M, Kaneko S. TSU-68 ameliorates hepatocellular carcinoma growth by inhibiting microenvironmental platelet-derived growth factor signaling. Anticancer Res. 2015 Mar;35(3):1423-31. PMID: 25750293. 2. Laird AD, Vajkoczy P, Shawver LK, Thurnher A, Liang C, Mohammadi M, Schlessinger J, Ullrich A, Hubbard SR, Blake RA, Fong TA, Strawn LM, Sun L, Tang C, Hawtin R, Tang F, Shenoy N, Hirth KP, McMahon G, Cherrington. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res. 2000 Aug 1;60(15):4152-60. PMID: 10945623.
In vivo protocol:
1. Yamamoto M, Kikuchi H, Ohta M, Kawabata T, Hiramatsu Y, Kondo K, Baba M, Kamiya K, Tanaka T, Kitagawa M, Konno H. TSU68 prevents liver metastasis of colon cancer xenografts by modulating the premetastatic niche. Cancer Res. 2008 Dec 1;68(23):9754-62. doi: 10.1158/0008-5472.CAN-08-1748. PMID: 19047154. 2. Marzola P, Degrassi A, Calderan L, Farace P, Crescimanno C, Nicolato E, Giusti A, Pesenti E, Terron A, Sbarbati A, Abrams T, Murray L, Osculati F. In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model. Clin Cancer Res. 2004 Jan 15;10(2):739-50. doi: 10.1158/1078-0432.ccr-0828-03. PMID: 14760097.
 1: Dong H, Ge D, Qu B, Zhu P, Wu Q, Wang T, Wang J, Li Z. Transarterial chemoembolization with or without multikinase inhibitors for patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis of randomized controlled trials. Front Oncol. 2023 Jun 8;13:1139025. doi: 10.3389/fonc.2023.1139025. PMID: 37361570; PMCID: PMC10285094. 2: Li H, Lan H, Li M, Pu X, Guo Y. A new molecular subclassification and in silico predictions for diagnosis and prognosis of papillary thyroid cancer by alternative splicing profile. Front Pharmacol. 2023 Mar 6;14:1119789. doi: 10.3389/fphar.2023.1119789. PMID: 36950012; PMCID: PMC10025316. 3: Das A, Prajapati A, Karna A, Sharma HK, Uppal S, Lather V, Pandita D, Agarwal P. Structure-based virtual screening of chemical libraries as potential MELK inhibitors and their therapeutic evaluation against breast cancer. Chem Biol Interact. 2023 May 1;376:110443. doi: 10.1016/j.cbi.2023.110443. Epub 2023 Mar 8. PMID: 36893906. 4: King NE, Courtney JM, Brown LS, Foster CG, Cashion JM, Attrill E, Premilovac D, Howells DW, Sutherland BA. Pharmacological PDGFRβ inhibitors imatinib and sunitinib cause human brain pericyte death in vitro. Toxicol Appl Pharmacol. 2022 Jun 1;444:116025. doi: 10.1016/j.taap.2022.116025. Epub 2022 Apr 17. PMID: 35443205. 5: Liu DY, Liu JC, Liang S, Meng XH, Greenbaum J, Xiao HM, Tan LJ, Deng HW. Drug Repurposing for COVID-19 Treatment by Integrating Network Pharmacology and Transcriptomics. Pharmaceutics. 2021 Apr 14;13(4):545. doi: 10.3390/pharmaceutics13040545. PMID: 33919660; PMCID: PMC8069812. 6: Yoshimatsu Y, Noguchi R, Tsuchiya R, Sei A, Sugaya J, Fukushima S, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-ASPS1-C1: a novel patient-derived cell line of alveolar soft-part sarcoma. Hum Cell. 2020 Oct;33(4):1302-1310. doi: 10.1007/s13577-020-00382-2. Epub 2020 Jul 10. PMID: 32648033. 7: Hidaka H, Izumi N, Aramaki T, Ikeda M, Inaba Y, Imanaka K, Okusaka T, Kanazawa S, Kaneko S, Kora S, Saito H, Furuse J, Matsui O, Yamashita T, Yokosuka O, Morita S, Arioka H, Kudo M, Arai Y. Subgroup analysis of efficacy and safety of orantinib in combination with TACE in Japanese HCC patients in a randomized phase III trial (ORIENTAL). Med Oncol. 2019 May 3;36(6):52. doi: 10.1007/s12032-019-1272-2. PMID: 31053989. 8: Kasak L, Näks M, Eek P, Piirsoo A, Bhadoria R, Starkov P, Saarma M, Kasvandik S, Piirsoo M. Characterization of Protein Kinase ULK3 Regulation by Phosphorylation and Inhibition by Small Molecule SU6668. Biochemistry. 2018 Sep 18;57(37):5456-5465. doi: 10.1021/acs.biochem.8b00356. Epub 2018 Sep 4. PMID: 30096229. 9: Kudo M, Arizumi T. Transarterial Chemoembolization in Combination with a Molecular Targeted Agent: Lessons Learned from Negative Trials (Post-TACE, BRISK-TA, SPACE, ORIENTAL, and TACE-2). Oncology. 2017;93 Suppl 1:127-134. doi: 10.1159/000481243. Epub 2017 Dec 20. PMID: 29258086. 10: Kudo M, Cheng AL, Park JW, Park JH, Liang PC, Hidaka H, Izumi N, Heo J, Lee YJ, Sheen IS, Chiu CF, Arioka H, Morita S, Arai Y. Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroenterol Hepatol. 2018 Jan;3(1):37-46. doi: 10.1016/S2468-1253(17)30290-X. Epub 2017 Oct 4. PMID: 28988687. 11: Tan H, Lei J, Xue L, Cai C, Liu QH, Shen J. Relaxing Effect of TSU-68, an Antiangiogenic Agent, on Mouse Airway Smooth Muscle. Cell Physiol Biochem. 2017;41(6):2350-2362. doi: 10.1159/000475653. Epub 2017 Apr 27. PMID: 28478457. 12: Qian B, Yao Y, Liu C, Zhang J, Chen H, Li H. SU6668 modulates prostate cancer progression by downregulating MTDH/AKT signaling pathway. Int J Oncol. 2017 May;50(5):1601-1611. doi: 10.3892/ijo.2017.3926. Epub 2017 Mar 22. PMID: 28339027; PMCID: PMC5403372. 13: Sohn BS, Kim SB, Ahn JH, Jung KH, Kim J, Lee KS, Ro J, Im SA, Im YH, Song HS, Park HS, Chung HC. Quality of life on TSU-68: Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline. Asia Pac J Clin Oncol. 2017 Dec;13(6):365-371. doi: 10.1111/ajco.12681. Epub 2017 Mar 16. PMID: 28303646. 14: Chen LT, Oh DY, Ryu MH, Yeh KH, Yeo W, Carlesi R, Cheng R, Kim J, Orlando M, Kang YK. Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review. Cancer Res Treat. 2017 Oct;49(4):851-868. doi: 10.4143/crt.2016.176. Epub 2017 Jan 3. PMID: 28052652; PMCID: PMC5654167. 15: Yoo C, Kim SB, Ro J, Im SA, Im YH, Kim JH, Ahn JH, Jung KH, Song HS, Kang SY, Park HS, Chung HC. Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in Patients with Metastatic Breast Cancer. Cancer Res Treat. 2016 Apr;48(2):499-507. doi: 10.4143/crt.2015.089. Epub 2015 Jul 14. PMID: 26194374; PMCID: PMC4843716. 16: Hara Y, Yamashita T, Oishi N, Nio K, Hayashi T, Nomura Y, Yoshida M, Hayashi T, Hashiba T, Asahina Y, Kondo M, Okada H, Sunagozaka H, Honda M, Kaneko S. TSU-68 ameliorates hepatocellular carcinoma growth by inhibiting microenvironmental platelet-derived growth factor signaling. Anticancer Res. 2015 Mar;35(3):1423-31. PMID: 25750293. 17: Chuma M, Terashita K, Sakamoto N. New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions. Hepatol Res. 2015 Oct;45(10):E1-E11. doi: 10.1111/hepr.12459. Epub 2015 Jan 9. PMID: 25472913. 18: Ikeda M, Shiina S, Nakachi K, Mitsunaga S, Shimizu S, Kojima Y, Ueno H, Morizane C, Kondo S, Sakamoto Y, Asaoka Y, Tateishi R, Koike K, Arioka H, Okusaka T. Phase I study on the safety, pharmacokinetic profile, and efficacy of the combination of TSU-68, an oral antiangiogenic agent, and S-1 in patients with advanced hepatocellular carcinoma. Invest New Drugs. 2014 Oct;32(5):928-36. doi: 10.1007/s10637-014-0109-2. Epub 2014 May 15. PMID: 24829073; PMCID: PMC4169869. 19: Kim SB, Yoo C, Ro J, Im SA, Im YH, Kim JH, Ahn JH, Jung KH, Song HS, Kang SY, Park HS, Chung HC. Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline: randomized phase II multicenter trial. Invest New Drugs. 2014 Aug;32(4):753-61. doi: 10.1007/s10637-014-0093-6. Epub 2014 Apr 9. PMID: 24715580. 20: Lee J, Shin SJ, Chung IJ, Kim TW, Chun HG, Shin DB, Kim YH, Song HS, Han SW, Kim JG, Kim SY, Choi YJ, Chung HC. A phase II open-label randomized multicenter trial of TSU-68 in combination with S-1 and oxaliplatin versus S-1 in combination with oxaliplatin in patients with metastatic colorectal cancer. Invest New Drugs. 2014 Jun;32(3):561-8. doi: 10.1007/s10637-014-0075-8. Epub 2014 Feb 27. PMID: 24573743.