WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406247
CAS#: 1202916-90-2 (free base)
Description: CX-6258 is a pan-Pim kinases inhibitor with excellent biochemical potency and kinase selectivity. CX-6258 exhibited in vitro synergy with chemotherapeutics and robust in vivo efficacy in two Pim kinases driven tumor models. Inhibition of Pim kinases is expected to have a beneficial effect as cancer therapy.
Hodoodo Cat#: H406247
Name: CX-6258
CAS#: 1202916-90-2 (free base)
Chemical Formula: C26H24ClN3O3
Exact Mass: 461.15
Molecular Weight: 461.940
Elemental Analysis: C, 67.60; H, 5.24; Cl, 7.67; N, 9.10; O, 10.39
Related CAS #: 1202916-90-2 (free base) 1353858-99-7 (HCl hydrate) 1353859-00-3 (HCl)
Synonym: CX6258; CX-6258; CX 6258.
IUPAC/Chemical Name: (E)-5-chloro-3-((5-(3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one
InChi Key: KGBPLKOPSFDBOX-CJLVFECKSA-N
InChi Code: InChI=1S/C26H24ClN3O3/c1-29-10-3-11-30(13-12-29)26(32)18-5-2-4-17(14-18)24-9-7-20(33-24)16-22-21-15-19(27)6-8-23(21)28-25(22)31/h2,4-9,14-16H,3,10-13H2,1H3,(H,28,31)/b22-16+
SMILES Code: O=C1NC2=C(C=C(Cl)C=C2)/C1=C\C3=CC=C(C4=CC=CC(C(N5CCN(C)CCC5)=O)=C4)O3
Appearance: orange 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# 1202916-90-2 (CX-6258 free base); 1353858-99-7 (CX-6258 HCl salt, hydrate).
| Biological target: | CX-6258 is a potent and kinase selective pan-Pim kinases inhibitor, with IC50s of 5 nM, 25 nM and 16 nM for Pim-1, Pim-2 and Pim-3, respectively. |
| In vitro activity: | CX-6258 shows antiproliferative activity against a panel of human cancer cell lines with IC50 of 0.02-3.7 μM, mostly sensitive to acute leukemia cell lines. Combinations of CX-6258 with doxorubicin (10:1 molar ratio) and CX-6258 with paclitaxel (100:1 molar ratio) produces synergistic cell killing with combination index (CI50) values equal to 0.4 and 0.56, respectively. CX-6258 causes dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively. Reference: ACS Med Chem Lett. 2011 Dec 27;3(2):135-9. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24900437/ |
| In vivo activity: | In an in vivo setting, analogue CX-6258 was evaluated in two human tumor xenograft growth efficacy models, acute myeloid leukemia MV-4-11, and prostate adenocarcinoma PC3. These particular models were selected because of the important roles that Pim kinases were shown to play in both diseases. Mice carrying MV-4-11 xenografts were administered a single oral dose daily. The drug exhibited dose dependent efficacy, with a 50 mg/kg dose producing 45% tumor growth inhibition (TGI) and a 100 mg/kg dose producing 75% TGI (Figure 4). Compound 13 was well tolerated throughout the study. Treatment of mice carrying PC3 xenografts once daily with a 50 mg/kg oral dose of CX-6258 was also well tolerated and produced 51% TGI (Supporting Information). Reference: ACS Med Chem Lett. 2011 Dec 27;3(2):135-9. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24900437/ |
The following data is based on the product molecular weight 461.94 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: | |
| In vitro protocol: | 1. Haddach M, Michaux J, Schwaebe MK, Pierre F, O'Brien SE, Borsan C, Tran J, Raffaele N, Ravula S, Drygin D, Siddiqui-Jain A, Darjania L, Stansfield R, Proffitt C, Macalino D, Streiner N, Bliesath J, Omori M, Whitten JP, Anderes K, Rice WG, Ryckman DM. Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor. ACS Med Chem Lett. 2011 Dec 27;3(2):135-9. doi: 10.1021/ml200259q. PMID: 24900437; PMCID: PMC4025662. 2. Melms JC, Vallabhaneni S, Mills CE, Yapp C, Chen JY, Morelli E, Waszyk P, Kumar S, Deming D, Moret N, Rodriguez S, Subramanian K, Rogava M, Cartwright ANR, Luoma A, Mei S, Brinker TJ, Miller DM, Spektor A, Schadendorf D, Riggi N, Wucherpfennig KW, Sorger PK, Izar B. Inhibition of Haspin Kinase Promotes Cell-Intrinsic and Extrinsic Antitumor Activity. Cancer Res. 2020 Feb 15;80(4):798-810. doi: 10.1158/0008-5472.CAN-19-2330. Epub 2019 Dec 27. PMID: 31882401; PMCID: PMC7029677. |
| In vivo protocol: | 1. Haddach M, Michaux J, Schwaebe MK, Pierre F, O'Brien SE, Borsan C, Tran J, Raffaele N, Ravula S, Drygin D, Siddiqui-Jain A, Darjania L, Stansfield R, Proffitt C, Macalino D, Streiner N, Bliesath J, Omori M, Whitten JP, Anderes K, Rice WG, Ryckman DM. Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor. ACS Med Chem Lett. 2011 Dec 27;3(2):135-9. doi: 10.1021/ml200259q. PMID: 24900437; PMCID: PMC4025662. |
1. Mustapha Haddach *, Jerome Michaux , Michael K. Schwaebe , Fabrice Pierre , Sean E. O’Brien , Cosmin Borsan , Joe Tran , Nicholas Raffaele , Suchitra Ravula , Denis Drygin , Adam Siddiqui-Jain , Levan Darjania , Ryan Stansfield , Chris Proffitt , Diwata Macalino , Nicole Streiner , Joshua Bliesath , May Omori , Jeffrey P. Whitten , Kenna Anderes , William G. Rice , and David M. Ryckman. ACS Med. Chem. Lett., 2012, 3 (2), pp 135–139.
