Olmutinib HCl | CAS# 1842366-97-5 | EGFR inhibitor

MedKoo Cat#: 412128 | Name: Olmutinib HCl

Description:

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

Olmutinib is a novel third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor, used in the treatment of T790M mutation positive non-small cell lung cancer. Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor. EGFRs are frequently over-expressed in lung cancer and contribute to activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways which both promote cell survival and proliferation. By inhibiting EGFR activation, Olmutinib attenuates the activation of these tumor-promoting pathways. In the first phase I/II clinical study of Osimertinib, 800 mg/ day was chosen as the dose for subsequent studies, and the dose-limiting toxicity and maximum tolerated dose was not reached. Olmutinib received breakthrough therapy designation in the United States in December 2015 and was approved for use in Korea in May 2016.

Chemical Structure

Olmutinib HCl

CAS#1842366-97-5 (2HCl)

Theoretical Analysis

MedKoo Cat#: 412128

Name: Olmutinib HCl

CAS#: 1842366-97-5 (2HCl)

Chemical Formula: C26H28Cl2N6O2S

Exact Mass: 0.0000

Molecular Weight: 559.51

Elemental Analysis: C, 55.81; H, 5.04; Cl, 12.67; N, 15.02; O, 5.72; S, 5.73

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

Bulk Inquiry

Related CAS #

1842366-97-5 (2HCl) 2102670-48-2 (HCl) 1353550-13-6 (free base) 2102714-68-9 (HCl hydrate)

Synonym

Olmutinib hydrochloride; BI-1482694 CL2; BI1482694 CL2; BI 1482694 CL2

IUPAC/Chemical Name

2-Propenamide, N-(3-((2-((4-(4-methyl-1-piperazinyl)phenyl)amino)thieno(3,2-d)pyrimidin-4-yl)oxy)phenyl)-, hydrochloride (1:2)

InChi Key

KIHHNWDWKMJZHH-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H26N6O2S.2ClH/c1-3-23(33)27-19-5-4-6-21(17-19)34-25-24-22(11-16-35-24)29-26(30-25)28-18-7-9-20(10-8-18)32-14-12-31(2)13-15-32;;/h3-11,16-17H,1,12-15H2,2H3,(H,27,33)(H,28,29,30);2*1H

SMILES Code

C=CC(NC1=CC=CC(OC2=C3C(C=CS3)=NC(NC4=CC=C(N5CCN(C)CC5)C=C4)=N2)=C1)=O.[H]Cl.[H]Cl

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

Shelf Life

>3 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

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 559.51 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.

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

1: Xiao Z, Chu C, Zhou L, Zhou Z, Zhang Q, Yang F, Yang Z, Zheng P, Xu S, Zhu W. Discovery of thiapyran-pyrimidine derivatives as potential EGFR inhibitors. Bioorg Med Chem. 2020 Oct 1;28(19):115669. doi: 10.1016/j.bmc.2020.115669. Epub 2020 Jul 28. PMID: 32912435. 2: Zhong J, Zhang J, Yu X, Zhang X, Dian L. Olmutinib Reverses Doxorubicin Resistance in ETS1-Overexpressing Leukemia Cells. Med Sci Monit. 2020 Aug 24;26:e924922. doi: 10.12659/MSM.924922. PMID: 32830792; PMCID: PMC7466836. 3: Xiao Z, Zhou Z, Chu C, Zhang Q, Zhou L, Yang Z, Li X, Yu L, Zheng P, Xu S, Zhu W. Design, synthesis and antitumor activity of novel thiophene-pyrimidine derivatives as EGFR inhibitors overcoming T790M and L858R/T790M mutations. Eur J Med Chem. 2020 Oct 1;203:112511. doi: 10.1016/j.ejmech.2020.112511. Epub 2020 Jul 6. PMID: 32679450. 4: Su Z, Yang T, Wang J, Lai M, Tong L, Wumaier G, Chen Z, Li S, Li H, Xie H, Zhao Z. Design, synthesis and biological evaluation of potent EGFR kinase inhibitors against 19D/T790M/C797S mutation. Bioorg Med Chem Lett. 2020 Aug 15;30(16):127327. doi: 10.1016/j.bmcl.2020.127327. Epub 2020 Jun 9. PMID: 32631532. 5: Chen Y, Yang L, Qiao H, Cheng Z, Xie J, Zhou W, Huang X, Jiang Y, Yu B, Zhao W. Discovery of new thieno[3,2-d]pyrimidine derivatives targeting EGFRL858R/T790M NSCLCs by the conformation constrained strategy. Eur J Med Chem. 2020 Aug 1;199:112388. doi: 10.1016/j.ejmech.2020.112388. Epub 2020 May 4. PMID: 32402937. 6: Lee J, Kim HS, Lee B, Kim HK, Sun JM, Ahn JS, Ahn MJ, Park K, Lee SH. Genomic landscape of acquired resistance to third-generation EGFR tyrosine kinase inhibitors in EGFR T790M-mutant non-small cell lung cancer. Cancer. 2020 Jun 1;126(11):2704-2712. doi: 10.1002/cncr.32809. Epub 2020 Mar 10. PMID: 32154925. 7: Kim SY, Lee JY, Kim DH, Joo H-, Yun MR, Jung D, Yun J, Heo SG, Ahn B-, Park CW, Pyo KH, Chun YJ, Hong MH, Kim HR, Cho BC. Patient-Derived Cells to Guide Targeted Therapy for Advanced Lung Adenocarcinoma. Sci Rep. 2019 Dec 27;9(1):19909. doi: 10.1038/s41598-019-56356-4. PMID: 31882684; PMCID: PMC6934824. 8: Attwa MW, Kadi AA, Abdelhameed AS. Detection and characterization of olmutinib reactive metabolites by LC-MS/MS: Elucidation of bioactivation pathways. J Sep Sci. 2020 Feb;43(4):708-718. doi: 10.1002/jssc.201900818. Epub 2019 Dec 2. PMID: 31788977. 9: Kim DW, Lee DH, Han JY, Lee J, Cho BC, Kang JH, Lee KH, Cho EK, Kim JS, Min YJ, Cho JY, An HJ, Kim HG, Lee KH, Kim BS, Jang IJ, Yoon S, Han O, Noh YS, Hong KY, Park K. Safety, tolerability, and anti-tumor activity of olmutinib in non- small cell lung cancer with T790M mutation: A single arm, open label, phase 1/2 trial. Lung Cancer. 2019 Sep;135:66-72. doi: 10.1016/j.lungcan.2019.07.007. Epub 2019 Jul 9. PMID: 31447004. 10: Noh YS, Yoon S, Kim SR, Lee KT, Jang IJ. A safety, pharmacokinetic, pharmacogenomic and population pharmacokinetic analysis of the third-generation EGFR TKI, olmutinib (HM61713), after single oral administration in healthy volunteers. Basic Clin Pharmacol Toxicol. 2019 Oct;125(4):370-381. doi: 10.1111/bcpt.13262. Epub 2019 Jun 28. PMID: 31125491. 11: Murtuza A, Bulbul A, Shen JP, Keshavarzian P, Woodward BD, Lopez-Diaz FJ, Lippman SM, Husain H. Novel Third-Generation EGFR Tyrosine Kinase Inhibitors and Strategies to Overcome Therapeutic Resistance in Lung Cancer. Cancer Res. 2019 Feb 15;79(4):689-698. doi: 10.1158/0008-5472.CAN-18-1281. Epub 2019 Feb 4. PMID: 30718357. 12: Roskoski R Jr. Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers. Pharmacol Res. 2019 Jan;139:395-411. doi: 10.1016/j.phrs.2018.11.014. Epub 2018 Nov 27. PMID: 30500458. 13: Zhang W, Fan YF, Cai CY, Wang JQ, Teng QX, Lei ZN, Zeng L, Gupta P, Chen ZS. Olmutinib (BI1482694/HM61713), a Novel Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Reverses ABCG2-Mediated Multidrug Resistance in Cancer Cells. Front Pharmacol. 2018 Oct 9;9:1097. doi: 10.3389/fphar.2018.01097. PMID: 30356705; PMCID: PMC6189370. 14: Zhang Z, Guo X, To KKW, Chen Z, Fang X, Luo M, Ma C, Xu J, Yan S, Fu L. Olmutinib (HM61713) reversed multidrug resistance by inhibiting the activity of ATP-binding cassette subfamily G member 2 in vitro and in vivo. Acta Pharm Sin B. 2018 Jul;8(4):563-574. doi: 10.1016/j.apsb.2018.06.002. Epub 2018 Jun 15. PMID: 30109181; PMCID: PMC6089862. 15: Oh SH, Byun HJ, Oh SJ, Jun JY, Park JH, Lee JH, Lee DY, Lee JH, Yang JM. Olmutinib Induced Lichen Planus Like Eruption. Ann Dermatol. 2018 Aug;30(4):451-453. doi: 10.5021/ad.2018.30.4.451. Epub 2018 Jun 27. PMID: 30065585; PMCID: PMC6029972. 16: Chen KL, Cho YT, Yang CW, Sheen YS, Liang CW, Lacouture ME, Chu CY. Olmutinib-induced palmoplantar keratoderma. Br J Dermatol. 2018 Feb;178(2):e129-e131. doi: 10.1111/bjd.15935. Epub 2017 Dec 18. PMID: 28869782; PMCID: PMC5812798. 17: Russo A, Franchina T, Ricciardi GRR, Smiroldo V, Picciotto M, Zanghì M, Rolfo C, Adamo V. Third generation EGFR TKIs in EGFR-mutated NSCLC: Where are we now and where are we going. Crit Rev Oncol Hematol. 2017 Sep;117:38-47. doi: 10.1016/j.critrevonc.2017.07.003. Epub 2017 Jul 5. PMID: 28807234. 18: Liao BC, Lin CC, Lee JH, Yang JC. Optimal management of EGFR-mutant non- small cell lung cancer with disease progression on first-line tyrosine kinase inhibitor therapy. Lung Cancer. 2017 Aug;110:7-13. doi: 10.1016/j.lungcan.2017.05.009. Epub 2017 May 11. PMID: 28676222. 19: Chen CW, Kuo CW, Chen YL, Ho CL, Su WC, Lin CC. Successful AZD9291 Therapy in Advanced Non-Small Cell Lung Cancer after Failure of HM61713. J Thorac Oncol. 2017 Jun;12(6):e72-e74. doi: 10.1016/j.jtho.2017.02.005. PMID: 28532566. 20: Juan O, Popat S. Treatment choice in epidermal growth factor receptor mutation-positive non-small cell lung carcinoma: latest evidence and clinical implications. Ther Adv Med Oncol. 2017 Mar;9(3):201-216. doi: 10.1177/1758834016687262. Epub 2017 Jan 30. PMID: 28344665; PMCID: PMC5349427.