CX-6258 HCl | CAS#1353859-00-3 | kinase inhibitor

MedKoo Cat#: 563398 | Name: CX-6258 HCl

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Description:

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

CX-6258 HCl is a potent, selective, and orally efficacious pan-Pim kinases inhibitor.

Chemical Structure

CX-6258 HCl

CAS#1353859-00-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 563398

Name: CX-6258 HCl

CAS#: 1353859-00-3 (HCl)

Chemical Formula: C26H25Cl2N3O3

Exact Mass: 0.0000

Molecular Weight: 498.40

Elemental Analysis: C, 62.66; H, 5.06; Cl, 14.23; N, 8.43; O, 9.63

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 315.00	2 Weeks
25mg	USD 750.00	2 weeks

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Related CAS #

1202916-90-2 (free base) 1353858-99-7 (HCl hydrate) 1353859-00-3 (HCl)

Synonym

CX-6258 Hydrochloride; CX 6258 Hydrochloride; CX6258 Hydrochloride; CX-6258 HCl; CX 6258 HCl; CX6258 HCl;

IUPAC/Chemical Name

(3E)-5-Chloro-3-[[5-[3-[(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)carbonyl]phenyl]-2-furanyl]methylene]-1,3-dihydro-2H-indol-2-one hydrochloride

InChi Key

YYIMMVXTWBIEAG-YHLMHSEJSA-N

InChi Code

InChI=1S/C26H24ClN3O3.ClH/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);1H/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.[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

2934.99.03.00

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

CX-6258 hydrochloride is a 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:

The Flt-3 IC50 values of analogues 13 (CX-6258) and 14 were therefore determined, and it was found that 13 and 14 inhibited Flt-3 with IC50 values of 0.134 μM and 0.150 μM, respectively. In addition, the Pim-3 IC50 values of both analogues were measured. Analogues 13 and 14 inhibited Pim-3 with IC50 values of 0.016 μM and greater than 1 μM, respectively. Since the Pim-3 isoform is overexpressed in pancreatic, gastric, and colon cancer, analogue 13 could be beneficial as an anticancer agent against these malignancies. Reference: ACS Med Chem Lett. 2012 Feb 9; 3(2): 135–139. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025662/

In vivo activity:

In an in vivo setting, analogue 13 (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). Reference: ACS Med Chem Lett. 2012 Feb 9; 3(2): 135–139. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025662/

	Solvent	mg/mL	mM
Solubility
	DMSO	57.0	114.37
	Ethanol	1.0	2.01

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 498.40 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. 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.

In vitro protocol:

In vivo protocol:

1: Fujii S, Nakamura S, Oda A, Miki H, Tenshin H, Teramachi J, Hiasa M, Bat-Erdene A, Maeda Y, Oura M, Takahashi M, Iwasa M, Endo I, Yoshida S, Aihara KI, Kurahashi K, Harada T, Kagawa K, Nakao M, Sano S, Abe M. Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity. Br J Haematol. 2018 Jan;180(2):246-258. doi: 10.1111/bjh.15033. PubMed PMID: 29327347. 2: Bogusz J, Zrubek K, Rembacz KP, Grudnik P, Golik P, Romanowska M, Wladyka B, Dubin G. Structural analysis of PIM1 kinase complexes with ATP-competitive inhibitors. Sci Rep. 2017 Oct 17;7(1):13399. doi: 10.1038/s41598-017-13557-z. PubMed PMID: 29042609; PubMed Central PMCID: PMC5645348. 3: Peterson BG, Tan KW, Osa-Andrews B, Iram SH. High-content screening of clinically tested anticancer drugs identifies novel inhibitors of human MRP1 (ABCC1). Pharmacol Res. 2017 May;119:313-326. doi: 10.1016/j.phrs.2017.02.024. Epub 2017 Feb 28. PubMed PMID: 28258008. 4: Rebello RJ, Kusnadi E, Cameron DP, Pearson HB, Lesmana A, Devlin JR, Drygin D, Clark AK, Porter L, Pedersen J, Sandhu S, Risbridger GP, Pearson RB, Hannan RD, Furic L. The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer. Clin Cancer Res. 2016 Nov 15;22(22):5539-5552. doi: 10.1158/1078-0432.CCR-16-0124. Epub 2016 Aug 2. PubMed PMID: 27486174. 5: Wang M, Tzintzun R, Gao M, Xu Z, Zheng QH. Synthesis of [11C]CX-6258 as a new PET tracer for imaging of Pim kinases in cancer. Bioorg Med Chem Lett. 2015 Sep 15;25(18):3831-5. doi: 10.1016/j.bmcl.2015.07.061. Epub 2015 Jul 26. PubMed PMID: 26227775. 6: Padmanabhan A, Gosc EB, Bieberich CJ. Stabilization of the prostate-specific tumor suppressor NKX3.1 by the oncogenic protein kinase Pim-1 in prostate cancer cells. J Cell Biochem. 2013 May;114(5):1050-7. doi: 10.1002/jcb.24444. PubMed PMID: 23129228. 7: 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. eCollection 2012 Feb 9. PubMed PMID: 24900437; PubMed Central PMCID: PMC4025662.