Pimasertib free base | CAS# 1236699-92-5 | MEK inhibitor

MedKoo Cat#: 200297 | Name: Pimasertib free base

Description:

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

Pimasertib (AS703026, SAR245509, MSC1936369B) is a selective, orally bioavailable inhibitor of MEK1/2 (mitogen-activated protein kinase kinase 1/2), key components of the MAPK/ERK signaling pathway implicated in various cancers. It exhibits potent inhibitory activity with an IC₅₀ of ~5 nM for MEK1 and ~6 nM for MEK2 in enzymatic assays. In cellular models, Pimasertib effectively suppresses ERK1/2 phosphorylation with sub-nanomolar to low nanomolar IC₅₀ values in BRAF- or RAS-mutant tumor cell lines. It has shown antiproliferative effects across multiple tumor types, particularly melanoma, colorectal, and pancreatic cancers, often inducing apoptosis or cell cycle arrest.

Chemical Structure

Pimasertib free base

CAS#1236699-92-5 (free base)

Theoretical Analysis

MedKoo Cat#: 200297

Name: Pimasertib free base

CAS#: 1236699-92-5 (free base)

Chemical Formula: C15H15FIN3O3

Exact Mass: 431.0142

Molecular Weight: 431.21

Elemental Analysis: C, 41.78; H, 3.51; F, 4.41; I, 29.43; N, 9.74; O, 11.13

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 1,950.00	2 Weeks
1g	USD 2,950.00	2 Weeks
2g	USD 5,450.00	2 Weeks

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Related CAS #

1236699-92-5 (free base) 1236361-78-6 (HCl)

Synonym

SAR245509; SAR-245509; SAR 245509; AS703026; AS 703026; AS-703026; MSC1936369B; MSC 1936369B; MSC-1936369B; Pimasertib;

IUPAC/Chemical Name

(S)-N-(2,3-dihydroxypropyl)-3-((2-fluoro-4-iodophenyl)amino)isonicotinamide.

InChi Key

VIUAUNHCRHHYNE-JTQLQIEISA-N

InChi Code

InChI=1S/C15H15FIN3O3/c16-12-5-9(17)1-2-13(12)20-14-7-18-4-3-11(14)15(23)19-6-10(22)8-21/h1-5,7,10,20-22H,6,8H2,(H,19,23)/t10-/m0/s1

SMILES Code

O=C(NC[C@H](O)CO)C1=CC=NC=C1NC2=CC=C(I)C=C2F

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

Related CAS# 1236699-92-5 (Pimasertib) 1236361-78-6 (Pimasertib Hydrochloride)

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Pimasertib (AS703026) is a highly selective, ATP non-competitive allosteric orally available MEK1/2 inhibitor.

In vitro activity:

AS703026 and AZD6244 were tested in various cell-based assays and tumor xenograft studies, focusing on isogenic human colorectal tumor cell lines that expressed only WT or mutant K-Ras (D-WT or D-MUT). The EGFR mAb cetuximab inhibited the Ras-ERK pathway and proliferation of D-WT cells in vitro and in vivo, but it did not inhibit proliferation of D-MUT cells in either setting. In contrast, AS703026 and AZD6244 effectively inhibited the growth of D-MUT cells in vitro and in vivo by specific inhibition of the key MEK downstream target kinase ERK. Inhibition of MEK by AS703026 or AZD6244 also suppressed cetuximab-resistant colorectal cancer cells attributed to K-ras mutation both in vitro and in vivo. Reference: Cancer Res. 2011 Jan 15;71(2):445-53. https://pubmed.ncbi.nlm.nih.gov/21118963/

In vivo activity:

AS703026 inhibited growth and survival of MM cells and cytokine-induced osteoclast differentiation more potently (9- to 10-fold) than AZD6244. Inhibition of proliferation induced by AS703026 was mediated by G0-G1 cell cycle arrest and was accompanied by reduction of MAF oncogene expression. AS703026 further induced apoptosis via caspase 3 and Poly ADP ribose polymerase (PARP) cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). Importantly, AS703026 sensitized MM cells to a broad spectrum of conventional (dexamethasone, melphalan), novel or emerging (lenalidomide, perifosine, bortezomib, rapamycin) anti-MM therapies. Significant tumour growth reduction in AS703026- vs. vehicle-treated mice bearing H929 MM xenograft tumours correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels in vivo. Reference: Br J Haematol. 2010 May;149(4):537-49. https://pubmed.ncbi.nlm.nih.gov/20331454/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	69.57
	DMSO	72.0	166.97
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.16
	Ethanol	1.0	2.32

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 431.21 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

Formulation protocol:

1. Yoon J, Koo KH, Choi KY. MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy. Cancer Res. 2011 Jan 15;71(2):445-53. doi: 10.1158/0008-5472.CAN-10-3058. Epub 2010 Nov 30. PMID: 21118963. 2. Kim K, Kong SY, Fulciniti M, Li X, Song W, Nahar S, Burger P, Rumizen MJ, Podar K, Chauhan D, Hideshima T, Munshi NC, Richardson P, Clark A, Ogden J, Goutopoulos A, Rastelli L, Anderson KC, Tai YT. Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo. Br J Haematol. 2010 May;149(4):537-49. doi: 10.1111/j.1365-2141.2010.08127.x. Epub 2010 Mar 12. PMID: 20331454; PMCID: PMC3418597. 3. Yoon J, Koo KH, Choi KY. MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy. Cancer Res. 2011 Jan 15;71(2):445-53. doi: 10.1158/0008-5472.CAN-10-3058. Epub 2010 Nov 30. PMID: 21118963. 4. Kim K, Kong SY, Fulciniti M, Li X, Song W, Nahar S, Burger P, Rumizen MJ, Podar K, Chauhan D, Hideshima T, Munshi NC, Richardson P, Clark A, Ogden J, Goutopoulos A, Rastelli L, Anderson KC, Tai YT. Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo. Br J Haematol. 2010 May;149(4):537-49. doi: 10.1111/j.1365-2141.2010.08127.x. Epub 2010 Mar 12. PMID: 20331454; PMCID: PMC3418597.

In vitro protocol:

In vivo protocol:

1: Lin D, Dong X, Xiao X, Xiang Z, Lei X, Wang J. Proteomic and phosphoproteomic analysis of responses to enterovirus A71 infection reveals novel targets for antiviral and viral replication. Antiviral Res. 2023 Dec;220:105761. doi: 10.1016/j.antiviral.2023.105761. Epub 2023 Nov 21. PMID: 37992763. 2: Alamri AM, Alkhilaiwi FA, Khan NU, Tasleem M. In silico Screening and Validation of Achyranthes aspera as a Potential Inhibitor of BRAF and NRAS in Controlling Thyroid Cancer. Anticancer Agents Med Chem. 2023;23(19):2111-2126. doi: 10.2174/1871520623666230607125258. PMID: 37287303. 3: Zhao C, Xiong K, Ji Z, Liu F, Li X. The Prognostic Value and Immunological Role of STEAP1 in Pan-Cancer: A Result of Data-Based Analysis. Oxid Med Cell Longev. 2022 Mar 11;2022:8297011. doi: 10.1155/2022/8297011. PMID: 35313641; PMCID: PMC8933652. 4: Lebbé C, Italiano A, Houédé N, Awada A, Aftimos P, Lesimple T, Dinulescu M, Schellens JHM, Leijen S, Rottey S, Kruse V, Kefford R, Raymond E, Faivre S, Pages C, Gomez-Roca C, Schueler A, Goodstal S, Massimini G, Delord JP. Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial. Target Oncol. 2021 Jan;16(1):47-57. doi: 10.1007/s11523-020-00767-1. PMID: 33211315. 5: Delord JP, Italiano A, Awada A, Aftimos P, Houédé N, Lebbé C, Pages C, Lesimple T, Dinulescu M, Schellens JHM, Leijen S, Rottey S, Kruse V, Kefford R, Faivre S, Gomez-Roca C, Scheuler A, Massimini G, Raymond E. Selective Oral MEK1/2 Inhibitor Pimasertib: A Phase I Trial in Patients with Advanced Solid Tumors. Target Oncol. 2021 Jan;16(1):37-46. doi: 10.1007/s11523-020-00768-0. PMID: 33170484. 6: Schneider P, Castro PG, Pinhanços SM, Kerstjens M, van Roon EH, Essing AHW, Dolman MEM, Molenaar JJ, Pieters R, Stam RW. Decitabine mildly attenuates MLL-rearranged acute lymphoblastic leukemia in vivo, and represents a poor chemo-sensitizer. EJHaem. 2020 Aug 24;1(2):527-536. doi: 10.1002/jha2.81. PMID: 35844991; PMCID: PMC9175850. 7: Lebbé C, Dutriaux C, Lesimple T, Kruit W, Kerger J, Thomas L, Guillot B, Braud F, Garbe C, Grob JJ, Loquai C, Ferraresi V, Robert C, Vasey P, Conry R, Isaacs R, Espinosa E, Schueler A, Massimini G, Dréno B. Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover. Cancers (Basel). 2020 Jun 29;12(7):1727. doi: 10.3390/cancers12071727. PMID: 32610581; PMCID: PMC7408351. 8: Ghanaatgar-Kasbi S, Khazaei M, Rastgar-Moghadam A, Ferns GA, Hassanian SM, Avan A. The Therapeutic Potential of MEK1/2 Inhibitors in the Treatment of Gynecological Cancers: Rational Strategies and Recent Progress. Curr Cancer Drug Targets. 2020;20(6):417-428. doi: 10.2174/1568009620666200424144303. PMID: 32329688. 9: Arend RC, Davis AM, Chimiczewski P, O'Malley DM, Provencher D, Vergote I, Ghamande S, Birrer MJ. EMR 20006-012: A phase II randomized double-blind placebo controlled trial comparing the combination of pimasertib (MEK inhibitor) with SAR245409 (PI3K inhibitor) to pimasertib alone in patients with previously treated unresectable borderline or low grade ovarian cancer. Gynecol Oncol. 2020 Feb;156(2):301-307. doi: 10.1016/j.ygyno.2019.12.002. Epub 2019 Dec 20. PMID: 31870556. 10: Yamazaki K, Doi T, Ikeda M, Okusaka T, Schueler A, Watanabe M, Ohtsu A. Phase I trial of pimasertib monotherapy in Japanese patients with solid tumors and those with hepatocellular carcinoma. Cancer Chemother Pharmacol. 2019 Nov;84(5):1027-1037. doi: 10.1007/s00280-019-03924-0. Epub 2019 Sep 3. PMID: 31482223. 11: Tarantelli C, Zhang L, Curti E, Gaudio E, Spriano F, Priebe V, Cascione L, Arribas AJ, Zucca E, Rossi D, Stathis A, Bertoni F. The Bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) demonstrated synergies with other anti- lymphoma targeted agents. Haematologica. 2019 Jul;104(7):e307-e309. doi: 10.3324/haematol.2018.214759. Epub 2019 Jan 24. PMID: 30679329; PMCID: PMC6601092. 12: de Weger VA, de Jonge M, Langenberg MHG, Schellens JHM, Lolkema M, Varga A, Demers B, Thomas K, Hsu K, Tuffal G, Goodstal S, Macé S, Deutsch E. A phase I study of the HDM2 antagonist SAR405838 combined with the MEK inhibitor pimasertib in patients with advanced solid tumours. Br J Cancer. 2019 Feb;120(3):286-293. doi: 10.1038/s41416-018-0355-8. Epub 2018 Dec 26. PMID: 30585255; PMCID: PMC6354023. 13: Schram AM, Gandhi L, Mita MM, Damstrup L, Campana F, Hidalgo M, Grande E, Hyman DM, Heist RS. A phase Ib dose-escalation and expansion study of the oral MEK inhibitor pimasertib and PI3K/MTOR inhibitor voxtalisib in patients with advanced solid tumours. Br J Cancer. 2018 Dec;119(12):1471-1476. doi: 10.1038/s41416-018-0322-4. Epub 2018 Nov 14. PMID: 30425349; PMCID: PMC6288157. 14: Dumas M, Laly P, Gottlieb J, Vercellino L, Paycha F, Bagot M, Baroudjian B, Madelaine I, Basset-Seguin N, Eftekhari P, Pagès C, Lebbé C, Lioté F. Osteopenia and fractures associated with long-term therapy with MEK inhibitors. Melanoma Res. 2018 Dec;28(6):641-644. doi: 10.1097/CMR.0000000000000490. PMID: 30124538. 15: Van Cutsem E, Hidalgo M, Canon JL, Macarulla T, Bazin I, Poddubskaya E, Manojlovic N, Radenkovic D, Verslype C, Raymond E, Cubillo A, Schueler A, Zhao C, Hammel P. Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer. Int J Cancer. 2018 Oct 15;143(8):2053-2064. doi: 10.1002/ijc.31603. Epub 2018 Aug 9. PMID: 29756206. 16: Er JL, Goh PN, Lee CY, Tan YJ, Hii LW, Mai CW, Chung FF, Leong CO. Identification of inhibitors synergizing gemcitabine sensitivity in the squamous subtype of pancreatic ductal adenocarcinoma (PDAC). Apoptosis. 2018 Jun;23(5-6):343-355. doi: 10.1007/s10495-018-1459-6. PMID: 29740790. 17: Vena F, Jia R, Esfandiari A, Garcia-Gomez JJ, Rodriguez-Justo M, Ma J, Syed S, Crowley L, Elenbaas B, Goodstal S, Hartley JA, Hochhauser D. MEK inhibition leads to BRCA2 downregulation and sensitization to DNA damaging agents in pancreas and ovarian cancer models. Oncotarget. 2018 Jan 22;9(14):11592-11603. doi: 10.18632/oncotarget.24294. PMID: 29545922; PMCID: PMC5837749. 18: Srinivas NR. Pharmacology of Pimasertib, A Selective MEK1/2 Inhibitor. Eur J Drug Metab Pharmacokinet. 2018 Aug;43(4):373-382. doi: 10.1007/s13318-018-0466-x. PMID: 29488172. 19: Lipponen A, El-Osta A, Kaspi A, Ziemann M, Khurana I, Kn H, Navarro- Ferrandis V, Puhakka N, Paananen J, Pitkänen A. Transcription factors Tp73, Cebpd, Pax6, and Spi1 rather than DNA methylation regulate chronic transcriptomics changes after experimental traumatic brain injury. Acta Neuropathol Commun. 2018 Feb 27;6(1):17. doi: 10.1186/s40478-018-0519-z. PMID: 29482641; PMCID: PMC5828078. 20: Faghfuri E, Nikfar S, Niaz K, Faramarzi MA, Abdollahi M. Mitogen-activated protein kinase (MEK) inhibitors to treat melanoma alone or in combination with other kinase inhibitors. Expert Opin Drug Metab Toxicol. 2018 Mar;14(3):317-330. doi: 10.1080/17425255.2018.1432593. Epub 2018 Jan 30. PMID: 29363351.