Tesevatinib
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MedKoo CAT#: 203186

CAS#: 781613-23-8

Description: Tesevatinib, also known as XL647, EXEL-7647 and KD-019, is a n orally bioavailable small-molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. XL647 binds to and inhibits several tyrosine receptor kinases that play major roles in tumor cell proliferation and tumor vascularization, including epidermal growth factor receptor (EGFR; ERBB1), epidermal growth factor receptor 2 (HER2; ERBB2), vascular endothelial growth factor receptor (VEGFR), and ephrin B4 (EphB4). This may result in the inhibition of tumor growth and angiogenesis, and tumor regression.

Chemical Structure

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Tesevatinib
CAS# 781613-23-8
Instruction

Theoretical Analysis

MedKoo Cat#: 203186
Name: Tesevatinib
CAS#: 781613-23-8
Chemical Formula: C24H25Cl2FN4O2
Exact Mass: 490.13
Molecular Weight: 491.385
Elemental Analysis: C, 58.66; H, 5.13; Cl, 14.43; F, 3.87; N, 11.40; O, 6.51

Price and Availability

Size Price Availability Quantity
1mg USD 265 2 Weeks
5mg USD 620 2 Weeks
10mg USD 1050 2 Weeks
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Related CAS #: 781613-23-8   874286-84-7    

Synonym: XL-647; XL 647; XL647; EXEL7647; EXEL-7647; EXEL7647; KD-019; KD019; KD 019.

IUPAC/Chemical Name: N-(3,4-dichloro-2-fluorophenyl)-6-methoxy-7-(((3aR,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl)methoxy)quinazolin-4-amine.

InChi Key: RTIZZWMBGKGLFO-YWQXDYITSA-N

InChi Code: InChI=1S/C39H38N4O5/c1-42-34(22-27-8-5-4-6-9-27)38(45)41-33(39(42)46)21-28-10-7-11-30(20-28)37(44)40-32-14-12-26(13-15-32)16-18-43-19-17-29-23-35(47-2)36(48-3)24-31(29)25-43/h4-15,20-24H,16-19,25H2,1-3H3,(H,40,44)(H,41,45)/b33-21-,34-22-

SMILES Code: O=C(NC1=CC=C(CCN2CC3=C(C=C(OC)C(OC)=C3)CC2)C=C1)C4=CC=CC(/C=C(C(N(C)/C5=C\C6=CC=CC=C6)=O)\NC5=O)=C4

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: 2934.99.9001

More Info: Phase II study of XL647: Forty-one patients were enrolled; 33 were evaluable for efficacy. One partial response was observed (response rate 3% and 90% confidence interval, 0% to 14%). Of patients whose tumors harbored T790M, 67% (8/12) had progression of disease as best response compared with 14% (3/21) of those without this mutation. Plasma samples from 40 patients were available for mutation testing, 14 (35%) of which were found to have EGFR mutations. CONCLUSIONS:  The 3% response rate observed did not meet the prespecified threshold to recommend further study of XL647 in patients who develop acquired resistance to erlotinib or gefitinib. Patients with T790M had a significantly worse progression-free survival.   (source: J Thorac Oncol. 2012 Jan;7(1):219-26.) Phase II study of XL647: Forty-one patients were enrolled; 33 were evaluable for efficacy. One partial response was observed (response rate 3% and 90% confidence interval, 0% to 14%). Of patients whose tumors harbored T790M, 67% (8/12) had progression of disease as best response compared with 14% (3/21) of those without this mutation. Plasma samples from 40 patients were available for mutation testing, 14 (35%) of which were found to have EGFR mutations. CONCLUSIONS:  The 3% response rate observed did not meet the prespecified threshold to recommend further study of XL647 in patients who develop acquired resistance to erlotinib or gefitinib. Patients with T790M had a significantly worse progression-free survival.    (source: J Thorac Oncol. 2012 Jan;7(1):219-26.)    

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 491.39 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:
In vitro protocol:
In vivo protocol:

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 1: Stasi I, Cappuzzo F. Second generation tyrosine kinase inhibitors for the treatment of metastatic non-small-cell lung cancer. Transl Respir Med. 2014 Jan 6;2:2. doi: 10.1186/2213-0802-2-2. eCollection 2014. PubMed PMID: 25505694; PubMed Central PMCID: PMC4215821.

2: Yu HA, Riely GJ. Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in lung cancers. J Natl Compr Canc Netw. 2013 Feb 1;11(2):161-9. PubMed PMID: 23411383; PubMed Central PMCID: PMC3673302.

3: Pietanza MC, Gadgeel SM, Dowlati A, Lynch TJ, Salgia R, Rowland KM Jr, Wertheim MS, Price KA, Riely GJ, Azzoli CG, Miller VA, Krug LM, Kris MG, Beumer JH, Tonda M, Mitchell B, Rizvi NA. Phase II study of the multitargeted tyrosine kinase inhibitor XL647 in patients with non-small-cell lung cancer. J Thorac Oncol. 2012 May;7(5):856-65. doi: 10.1097/JTO.0b013e31824c943f. PubMed PMID: 22722787.

4: Chmielecki J, Pietanza MC, Aftab D, Shen R, Zhao Z, Chen X, Hutchinson K, Viale A, Kris MG, Stout T, Miller V, Rizvi N, Pao W. EGFR-mutant lung adenocarcinomas treated first-line with the novel EGFR inhibitor, XL647, can subsequently retain moderate sensitivity to erlotinib. J Thorac Oncol. 2012 Feb;7(2):434-42. doi: 10.1097/JTO.0b013e31823c5aee. PubMed PMID: 22173702; PubMed Central PMCID: PMC3261336.

5: Pietanza MC, Lynch TJ Jr, Lara PN Jr, Cho J, Yanagihara RH, Vrindavanam N, Chowhan NM, Gadgeel SM, Pennell NA, Funke R, Mitchell B, Wakelee HA, Miller VA. XL647--a multitargeted tyrosine kinase inhibitor: results of a phase II study in subjects with non-small cell lung cancer who have progressed after responding to treatment with either gefitinib or erlotinib. J Thorac Oncol. 2012 Jan;7(1):219-26. doi: 10.1097/JTO.0b013e31822eebf9. PubMed PMID: 22011666.

6: Gaughan EM, Costa DB. Genotype-driven therapies for non-small cell lung cancer: focus on EGFR, KRAS and ALK gene abnormalities. Ther Adv Med Oncol. 2011 May;3(3):113-25. doi: 10.1177/1758834010397569. PubMed PMID: 21904575; PubMed Central PMCID: PMC3150063.

7: Giaccone G, Wang Y. Strategies for overcoming resistance to EGFR family tyrosine kinase inhibitors. Cancer Treat Rev. 2011 Oct;37(6):456-64. doi: 10.1016/j.ctrv.2011.01.003. Epub 2011 Mar 1. Review. PubMed PMID: 21367530; PubMed Central PMCID: PMC3139833.

8: Nguyen KS, Kobayashi S, Costa DB. Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer. 2009 Jul;10(4):281-9. doi: 10.3816/CLC.2009.n.039. Review. PubMed PMID: 19632948; PubMed Central PMCID: PMC2758558.

9: Pakkala S, Ramalingam SS. Combined inhibition of vascular endothelial growth factor and epidermal growth factor signaling in non-small-cell lung cancer therapy. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S17-23. doi: 10.3816/CLC.2009.s.003. Review. PubMed PMID: 19362942.

10: Pennell NA, Lynch TJ Jr. Combined inhibition of the VEGFR and EGFR signaling pathways in the treatment of NSCLC. Oncologist. 2009 Apr;14(4):399-411. doi: 10.1634/theoncologist.2008-0276. Epub 2009 Apr 8. Review. PubMed PMID: 19357226.

11: Riely GJ. Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. J Thorac Oncol. 2008 Jun;3(6 Suppl 2):S146-9. doi: 10.1097/JTO.0b013e318174e96e. Review. PubMed PMID: 18520300.

12: Cabebe E, Wakelee H. Role of anti-angiogenesis agents in treating NSCLC: focus on bevacizumab and VEGFR tyrosine kinase inhibitors. Curr Treat Options Oncol. 2007 Feb;8(1):15-27. Review. PubMed PMID: 17634832.

13: Gendreau SB, Ventura R, Keast P, Laird AD, Yakes FM, Zhang W, Bentzien F, Cancilla B, Lutman J, Chu F, Jackman L, Shi Y, Yu P, Wang J, Aftab DT, Jaeger CT, Meyer SM, De Costa A, Engell K, Chen J, Martini JF, Joly AH. Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647. Clin Cancer Res. 2007 Jun 15;13(12):3713-23. PubMed PMID: 17575237.