Asciminib free base
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MedKoo CAT#: 206490

CAS#: 1492952-76-7 (free base)

Description: Asciminib, also known as ABL001, is a potent allosteric inhibitor of BCR-ABL. ABL001 prevents emergence of resistant disease when administered in combination with nilotinib in an in vivo murine model of chronic myeloid leukemia. Cell proliferation studies demonstrate that ABL001 selectively inhibited the growth of CML and Ph+ ALL cells with potencies ranging from 1-10nM range. ABL001 was tested for activity against clinically observed mutations and found to be active in the low nM range. In the KCL-22 mouse xenograft model, ABL001 displayed potent anti-tumor activity with complete tumor regression observed and a clear dose-dependent correlation with pSTAT5 inhibition.


Chemical Structure

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Asciminib free base
CAS# 1492952-76-7 (free base)

Theoretical Analysis

MedKoo Cat#: 206490
Name: Asciminib free base
CAS#: 1492952-76-7 (free base)
Chemical Formula: C20H18ClF2N5O3
Exact Mass: 449.1066
Molecular Weight: 449.8428
Elemental Analysis: C, 53.40; H, 4.03; Cl, 7.88; F, 8.45; N, 15.57; O, 10.67

Size Price Shipping out time Quantity
5mg USD 82 Same day
10mg USD 150 Same day
25mg USD 310 Same day
50mg USD 550 Same day
100mg USD 950 Same day
200mg USD 1450 Same day
500mg USD 2250 Same day
1g USD 3250 Same day
2g USD 5850 2 Weeks
Inquire bulk and customized quantity

Pricing updated 2021-03-06. Prices are subject to change without notice.

Asciminib free base, purity > 98%, is in stock. The same day shipping after order is received.

Related CAS #: 1492952-76-7 (free base)   2119669-71-3 (HCl)    

Synonym: ABL-001; AB -001; ABL001; asciminib; asciminib free base;

IUPAC/Chemical Name: (R)-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide

InChi Key: VOVZXURTCKPRDQ-CQSZACIVSA-N

InChi Code: InChI=1S/C20H18ClF2N5O3/c21-20(22,23)31-15-3-1-13(2-4-15)26-19(30)12-9-16(17-5-7-25-27-17)18(24-10-12)28-8-6-14(29)11-28/h1-5,7,9-10,14,29H,6,8,11H2,(H,25,27)(H,26,30)/t14-/m1/s1

SMILES Code: O=C(NC1=CC=C(OC(F)(Cl)F)C=C1)C2=CN=C(N3C[C@H](O)CC3)C(C4=CC=NN4)=C2

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

Preparing Stock Solutions

The following data is based on the product molecular weight 449.8428 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.

Select a batch to recalculate based on the batch molecular weight:
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

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1: Tran P, Hanna I, Eggimann FK, Schoepfer J, Ray T, Zhu B, Wang L, Priess P, Tian X, Hourcade-Potelleret F, Einolf HJ. Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects. Xenobiotica. 2019 Apr 22:1-20. doi: 10.1080/00498254.2019.1594449. [Epub ahead of print] PubMed PMID: 31006307.

2: Zhan JY, Ma J, Zheng QC. Molecular dynamics investigation on the Asciminib resistance mechanism of I502L and V468F mutations in BCR-ABL. J Mol Graph Model. 2019 Jun;89:242-249. doi: 10.1016/j.jmgm.2019.03.018. Epub 2019 Mar 21. PubMed PMID: 30927708.

3: El Rashedy AA, Appiah-Kubi P, Soliman MES. A Synergistic Combination Against Chronic Myeloid Leukemia: An Intra-molecular Mechanism of Communication in BCR-ABL1 Resistance. Protein J. 2019 Apr;38(2):142-150. doi: 10.1007/s10930-019-09820-z. PubMed PMID: 30877503.

4: Singh AP, Glennon MS, Umbarkar P, Gupte M, Galindo CL, Zhang Q, Force T, Becker JR, Lal H. Ponatinib-induced cardiotoxicity: delineating the signalling mechanisms and potential rescue strategies. Cardiovasc Res. 2019 Apr 15;115(5):966-977. doi: 10.1093/cvr/cvz006. PubMed PMID: 30629146; PubMed Central PMCID: PMC6452321.

5: Schoepfer J, Jahnke W, Berellini G, Buonamici S, Cotesta S, Cowan-Jacob SW, Dodd S, Drueckes P, Fabbro D, Gabriel T, Groell JM, Grotzfeld RM, Hassan AQ, Henry C, Iyer V, Jones D, Lombardo F, Loo A, Manley PW, Pellé X, Rummel G, Salem B, Warmuth M, Wylie AA, Zoller T, Marzinzik AL, Furet P. Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. J Med Chem. 2018 Sep 27;61(18):8120-8135. doi: 10.1021/acs.jmedchem.8b01040. Epub 2018 Sep 7. PubMed PMID: 30137981.

6: Menssen HD, Quinlan M, Kemp C, Tian X. Relative Bioavailability and Food Effect Evaluation for 2 Tablet Formulations of Asciminib in a 2-Arm, Crossover, Randomized, Open-Label Study in Healthy Volunteers. Clin Pharmacol Drug Dev. 2019 Apr;8(3):385-394. doi: 10.1002/cpdd.602. Epub 2018 Jul 30. PubMed PMID: 30059193.

7: Zanforlin E, Zagotto G, Ribaudo G. A Chemical Approach to Overcome Tyrosine Kinase Inhibitors Resistance : Learning from Chronic Myeloid Leukemia. Curr Med Chem. 2018 Jun 6. doi: 10.2174/0929867325666180607092451. [Epub ahead of print] PubMed PMID: 29874990.

8: Eadie LN, Saunders VA, Branford S, White DL, Hughes TP. The new allosteric inhibitor asciminib is susceptible to resistance mediated by ABCB1 and ABCG2 overexpression in vitro. Oncotarget. 2018 Feb 3;9(17):13423-13437. doi: 10.18632/oncotarget.24393. eCollection 2018 Mar 2. PubMed PMID: 29568367; PubMed Central PMCID: PMC5862588.

9: Massaro F, Colafigli G, Molica M, Breccia M. Novel tyrosine-kinase inhibitors for the treatment of chronic myeloid leukemia: safety and efficacy. Expert Rev Hematol. 2018 Apr;11(4):301-306. doi: 10.1080/17474086.2018.1451322. Epub 2018 Mar 13. Review. PubMed PMID: 29522367.

10: El Rashedy AA, Olotu FA, Soliman MES. Dual Drug Targeting of Mutant Bcr-Abl Induces Inactive Conformation: New Strategy for the Treatment of Chronic Myeloid Leukemia and Overcoming Monotherapy Resistance. Chem Biodivers. 2018 Mar;15(3):e1700533. doi: 10.1002/cbdv.201700533. Epub 2018 Mar 7. PubMed PMID: 29325229.

11: Qiang W, Antelope O, Zabriskie MS, Pomicter AD, Vellore NA, Szankasi P, Rea D, Cayuela JM, Kelley TW, Deininger MW, O'Hare T. Mechanisms of resistance to the BCR-ABL1 allosteric inhibitor asciminib. Leukemia. 2017 Dec;31(12):2844-2847. doi: 10.1038/leu.2017.264. Epub 2017 Aug 18. PubMed PMID: 28819281.

12: Romero D. Haematological cancer: Dual targeting to defeat resistance. Nat Rev Clin Oncol. 2017 Jun;14(6):328-329. doi: 10.1038/nrclinonc.2017.58. Epub 2017 Apr 11. PubMed PMID: 28397824.

13: Sarosiek K. Double trouble for CML. Sci Transl Med. 2017 Apr 5;9(384). pii: e2773. doi: 10.1126/scitranslmed.aan2773. PubMed PMID: 28381535.

14: Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, Marzinzik AL, Pelle X, Donovan J, Zhu W, Buonamici S, Hassan AQ, Lombardo F, Iyer V, Palmer M, Berellini G, Dodd S, Thohan S, Bitter H, Branford S, Ross DM, Hughes TP, Petruzzelli L, Vanasse KG, Warmuth M, Hofmann F, Keen NJ, Sellers WR. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature. 2017 Mar 30;543(7647):733-737. doi: 10.1038/nature21702. Epub 2017 Mar 22. PubMed PMID: 28329763.