Telatinib
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MedKoo CAT#: 206424

CAS#: 332012-40-5

Description: Telatinib, also known as BAY 57-9352, is a potent and orally active VEGFR-2 and VEGFR-3 tyrosine kinase inhibitor. Telatinib reverses chemotherapeutic multidrug resistance mediated by ABCG2 efflux transporter in vitro and in vivo. Telatinib treatment was well tolerated. The observed single agent antitumor activity in heavily pretreated CRC patients was limited. Pharmacodynamic results are suggestive for the biological activity of telatinib justifying a further evaluation of telatinib bid in combination with standard chemotherapy regimens in CRC patients.

Chemical Structure

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Telatinib
CAS# 332012-40-5
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206424
Name: Telatinib
CAS#: 332012-40-5
Chemical Formula: C20H16ClN5O3
Exact Mass: 409.09
Molecular Weight: 409.830
Elemental Analysis: C, 58.61; H, 3.94; Cl, 8.65; N, 17.09; O, 11.71

Price and Availability

Size Price Availability Quantity
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1250 Ready to ship
1g USD 1850 Ready to ship
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Synonym: BAY 57-9352; BAY 57-9352; BAY57-9352; Telatinib.

IUPAC/Chemical Name: 4-(((4-((4-chlorophenyl)amino)furo[2,3-d]pyridazin-7-yl)oxy)methyl)-N-methylpicolinamide

InChi Key: QFCXANHHBCGMAS-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H16ClN5O3/c1-22-19(27)16-10-12(6-8-23-16)11-29-20-17-15(7-9-28-17)18(25-26-20)24-14-4-2-13(21)3-5-14/h2-10H,11H2,1H3,(H,22,27)(H,24,25)

SMILES Code: O=C(C1=NC=CC(COC2=NN=C(NC3=CC=C(Cl)C=C3)C4=C2OC=C4)=C1)NC

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: >2 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: 2934.99.03.00

More Info:

Biological target: Telatinib (Bay 57-9352) is an inhibitor of VEGFR2, VEGFR3, PDGFα, and c-Kit with IC50s of 6, 4, 15 and 1 nM, respectively.
In vitro activity: Telatinib increased the accumulation of MX and decreased the efflux rate in cells transfected with ABCG2. Furthermore, telatinib did not affect either expression or localization of ABCG2. However, effect of telatinib on localization still needs to be confirmed by more sensitive means. It indicates that increase in MX levels in the cells expressing ABCG2 is because of inhibition of ABCG2 drug efflux function by telatinib. Telatinib stimulated the ABCG2 ATPase activity in a concentration dependent manner. In addition telatinib effectively reduced the ATP-dependent uptake of [3H]-E217βG in membrane vesicles obtained from ABCG2-482-R2 without affecting the uptake in the parental HEK293/pcDNA3.1 vesicles. This shows the ability of telatinib to directly interact with the ABCG2 membrane transporter and thereafter inhibiting its transport activity at sub-micromolar concentrations. Reference: Biochem Pharmacol. 2014 May 1; 89(1): 52–61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983711/
In vivo activity: The H460/MX20 tumor growth rate recorded over a period of 18 days was significantly slow in the telatinib-DOX combination group compared to vehicle, telatinib alone or DOX alone groups (Fig. 6B). In addition, telatinib in combination with DOX also produced a significant reduction in tumor size and weight (Fig. 6D and ​7B). It should be noted that telatinib by itself also significantly decreased the growth rate of H460 and H460/MX20 xenografts. However, there was no significant difference between the effects of telatinib alone or combination on the H460 xenografts (Fig. 6A, 6C and ​and7A).7A). DOX with or without telatinib did not produce any apparent toxicity or weight loss (Fig. 7C). Immunohistochemical analysis of the excised tumors showed expression of ABCG2 in H460/MX20 tumors and there was no significant difference in the expression level of the ABCG2 among different groups. Taken together, telatinib did not increase the toxicity; instead it improved the efficacy of DOX in the H460/MX20 xenograft model. Reference: Biochem Pharmacol. 2014 May 1; 89(1): 52–61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983711/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 44.3 108.17
DMSO:PBS (pH 7.2) (1:2) 0.3 0.81
DMF 5.0 12.20

Preparing Stock Solutions

The following data is based on the product molecular weight 409.83 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. Sodani K, Patel A, Anreddy N, Singh S, Yang DH, Kathawala RJ, Kumar P, Talele TT, Chen ZS. Telatinib reverses chemotherapeutic multidrug resistance mediated by ABCG2 efflux transporter in vitro and in vivo. Biochem Pharmacol. 2014 May 1;89(1):52-61. doi: 10.1016/j.bcp.2014.02.012. Epub 2014 Feb 22. PMID: 24565910; PMCID: PMC3983711.
In vitro protocol: 1. Sodani K, Patel A, Anreddy N, Singh S, Yang DH, Kathawala RJ, Kumar P, Talele TT, Chen ZS. Telatinib reverses chemotherapeutic multidrug resistance mediated by ABCG2 efflux transporter in vitro and in vivo. Biochem Pharmacol. 2014 May 1;89(1):52-61. doi: 10.1016/j.bcp.2014.02.012. Epub 2014 Feb 22. PMID: 24565910; PMCID: PMC3983711.
In vivo protocol: 1. Sodani K, Patel A, Anreddy N, Singh S, Yang DH, Kathawala RJ, Kumar P, Talele TT, Chen ZS. Telatinib reverses chemotherapeutic multidrug resistance mediated by ABCG2 efflux transporter in vitro and in vivo. Biochem Pharmacol. 2014 May 1;89(1):52-61. doi: 10.1016/j.bcp.2014.02.012. Epub 2014 Feb 22. PMID: 24565910; PMCID: PMC3983711.

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1: Wang YJ, Zhang YK, Kathawala RJ, Chen ZS. Repositioning of Tyrosine Kinase Inhibitors as Antagonists of ATP-Binding Cassette Transporters in Anticancer Drug Resistance. Cancers (Basel). 2014 Sep 29;6(4):1925-52. doi: 10.3390/cancers6041925. Review. PubMed PMID: 25268163; PubMed Central PMCID: PMC4276951.

2: Sodani K, Patel A, Anreddy N, Singh S, Yang DH, Kathawala RJ, Kumar P, Talele TT, Chen ZS. Telatinib reverses chemotherapeutic multidrug resistance mediated by ABCG2 efflux transporter in vitro and in vivo. Biochem Pharmacol. 2014 May 1;89(1):52-61. doi: 10.1016/j.bcp.2014.02.012. Epub 2014 Feb 22. PubMed PMID: 24565910; PubMed Central PMCID: PMC3983711.

3: Benjamin B, Sahu M, Bhatnagar U, Abhyankar D, Srinivas NR. The observed correlation between in vivo clinical pharmacokinetic parameters and in vitro potency of VEGFR-2 inhibitors. Can this be used as a prospective guide for the development of novel compounds? Arzneimittelforschung. 2012 Apr;62(4):194-201. doi: 10.1055/s-0031-1299772. Epub 2012 Jan 30. PubMed PMID: 22290114.

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6: Xie Q, Wondergem R, Shen Y, Cavey G, Ke J, Thompson R, Bradley R, Daugherty-Holtrop J, Xu Y, Chen E, Omar H, Rosen N, Wenkert D, Xu HE, Vande Woude GF. Benzoquinone ansamycin 17AAG binds to mitochondrial voltage-dependent anion channel and inhibits cell invasion. Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4105-10. doi: 10.1073/pnas.1015181108. Epub 2011 Feb 22. Erratum in: Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5472. Daughtery-Holtrop, Jennifer [corrected to Daugherty-Holtrop, Jennifer]. PubMed PMID: 21368131; PubMed Central PMCID: PMC3053964.

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8: Langenberg MH, Witteveen PO, Roodhart JM, Verheul HM, Mergui-Roelvink M, van der Sar J, Brendel E, Laferriere N, Schellens JH, Voest EE. Phase I evaluation of telatinib, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in combination with irinotecan and capecitabine in patients with advanced solid tumors. Clin Cancer Res. 2010 Apr 1;16(7):2187-97. doi: 10.1158/1078-0432.CCR-09-2436. Epub 2010 Mar 16. PubMed PMID: 20233884.

9: Steeghs N, Gelderblom H, Wessels J, Eskens FA, de Bont N, Nortier JW, Guchelaar HJ. Pharmacogenetics of telatinib, a VEGFR-2 and VEGFR-3 tyrosine kinase inhibitor, used in patients with solid tumors. Invest New Drugs. 2011 Feb;29(1):137-43. doi: 10.1007/s10637-009-9347-0. Epub 2009 Nov 19. PubMed PMID: 19924384; PubMed Central PMCID: PMC3016151.

10: Eskens FA, Steeghs N, Verweij J, Bloem JL, Christensen O, van Doorn L, Ouwerkerk J, de Jonge MJ, Nortier JW, Kraetzschmar J, Rajagopalan P, Gelderblom H. Phase I dose escalation study of telatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 3, platelet-derived growth factor receptor beta, and c-Kit, in patients with advanced or metastatic solid tumors. J Clin Oncol. 2009 Sep 1;27(25):4169-76. doi: 10.1200/JCO.2008.18.8193. Epub 2009 Jul 27. PubMed PMID: 19636022.

11: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Oct;30(8):643-72. PubMed PMID: 19088949.

12: Strumberg D, Schultheis B, Adamietz IA, Christensen O, Buechert M, Kraetzschmar J, Rajagopalan P, Ludwig M, Frost A, Steinbild S, Scheulen ME, Mross K. Phase I dose escalation study of telatinib (BAY 57-9352) in patients with advanced solid tumours. Br J Cancer. 2008 Nov 18;99(10):1579-85. doi: 10.1038/sj.bjc.6604724. PubMed PMID: 19002179; PubMed Central PMCID: PMC2584942.

13: Steeghs N, Gelderblom H, Roodt JO, Christensen O, Rajagopalan P, Hovens M, Putter H, Rabelink TJ, de Koning E. Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor. Clin Cancer Res. 2008 Jun 1;14(11):3470-6. doi: 10.1158/1078-0432.CCR-07-5050. PubMed PMID: 18519779.

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