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MedKoo Cat#: 205768 | Name: BMS-863233 HCl
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Description:

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

BMS-863233, also known as XL-413, is an orally bioavailable cell division cycle 7 homolog (CDC7) kinase inhibitor with potential antineoplastic activity. CDC7 kinase inhibitor BMS-863233 binds to and inhibits the activity of CDC7, which may result in the inhibition of DNA replication and mitosis, the induction of tumor cell apoptosis, and the inhibition of tumor cell proliferation in CDC7-overexpressing tumor cells. CDC7, a serine-threonine kinase overexpressed in a variety of tumor cell types, plays an essential role in the initiation of DNA replication by activating origins of replication.

Chemical Structure

BMS-863233 HCl
BMS-863233 HCl
CAS#1169562-71-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 205768

Name: BMS-863233 HCl

CAS#: 1169562-71-3 (HCl)

Chemical Formula: C14H12ClN3O2

Exact Mass: 289.0618

Molecular Weight: 289.72

Elemental Analysis: C, 58.04; H, 4.17; Cl, 12.24; N, 14.50; O, 11.04

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,650.00 Ready to Ship
1g USD 4,250.00 Ready to Ship
2g USD 7,450.00 Ready to Ship
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Related CAS #
1169562-71-3 (HCl) 1169558-38-6 (free base)
Synonym
BMS863233; BMS-863233; BMS 863233; XL413; XL-413; XL 413.
IUPAC/Chemical Name
(S)-8-chloro-2-(pyrrolidin-2-yl)benzofuro[3,2-d]pyrimidin-4(3H)-one hydrochloride
InChi Key
UNDKJUKLBNARIZ-FVGYRXGTSA-N
InChi Code
InChI=1S/C14H12ClN3O2.ClH/c15-7-3-4-10-8(6-7)11-12(20-10)14(19)18-13(17-11)9-2-1-5-16-9;/h3-4,6,9,16H,1-2,5H2,(H,17,18,19);1H/t9-;/m0./s1
SMILES Code
O=C1C(OC2=CC=C(Cl)C=C23)=C3N=C([C@H]4NCCC4)N1.[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 water, ethanol, slightly soluble in DMSO.
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in water or ethanol, or DMSO-water.
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:   1169562-71-3 (BMS-863233 HCl salt) 1169558-38-6 (BMS-863233 free base).  
Biological target:
XL413 hydrochloride is a potent, selective and ATP competitive inhibitor of Cdc7, with an IC50 of 3.4 nM, and also shows potent effect with IC50s of 215, 42 nM on CK2, PIM1, respectively, and an EC50 of 118 nM on pMCM.
In vitro activity:
XL413 treatment after editing produced a dose-dependent increase in HR (homologous recombination) efficiency at each locus in T cells (Fig. 4a), without evidence of decreased viability (Supplementary Fig. 4a). Using a ssDonor template and targeting five additional genomic loci, XL413 also boosts SSTR in human T cells while NHEJ frequencies decreased (Fig. 4b and Supplementary Data 2). This shows that CDC7 inhibition does not affect the total amount of editing but rather shifts the ratio of edited alleles from NHEJ (non-homologous end joining factor) to HDR (homology directed repair). Furthermore, treatment with XL413 increased SSTR (single strand template repair) beyond 60% efficiency when introducing a naturally occurring SNP (single nucleotide polymorphism) that alters recognition of CD4 by the OKT4 antibody without affecting recognition by the SK3 antibody26 (Fig. 4c and Supplementary Fig. 4b–d). Reference: Nat Commun. 2020; 11: 2109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193628/
In vivo activity:
Multiple-dose studies of 14 (XL413) in a Colo-205 xenograft model demonstrates significant anti-tumor efficacy. Tumor bearing mice were administered 14 orally at doses of 10, 30, or 100 mg/kg once daily (qd) for 14 days (Fig. 5). Two alternate dosing regimens were also examined in this study: a dose of 30 mg/kg administered twice-daily (bid) and a dose of 100 mg/kg administered every-other day (q2d). Compound 14 was well tolerated at all the doses and regimens examined, with no significant body weight loss observed. Only modest tumor growth inhibition (36%) was observed for the 10 mg/kg qd dosage, but significant tumor growth inhibition (83%) was observed at the 30 mg/kg qd dose. More impressively, significant tumor growth regression (32%) was observed if dosed twice-daily at 30 mg/kg. The ED50 is estimated at 13 mg/kg. Reference: Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31. https://pubmed.ncbi.nlm.nih.gov/22560567/
Solvent mg/mL mM
Solubility
DMSO 1.8 6.12
Water 8.3 28.51
PBS (pH 7.2) 10.0 34.52
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 289.72 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.

Recalculate based on batch purity %
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. Wienert B, Nguyen DN, Guenther A, Feng SJ, Locke MN, Wyman SK, Shin J, Kazane KR, Gregory GL, Carter MAM, Wright F, Conklin BR, Marson A, Richardson CD, Corn JE. Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair. Nat Commun. 2020 Apr 30;11(1):2109. doi: 10.1038/s41467-020-15845-1. PMID: 32355159; PMCID: PMC7193628. 2. Jin S, Ma H, Yang W, Ju H, Wang L, Zhang Z. Cell division cycle 7 is a potential therapeutic target in oral squamous cell carcinoma and is regulated by E2F1. J Mol Med (Berl). 2018 Jun;96(6):513-525. doi: 10.1007/s00109-018-1636-7. Epub 2018 Apr 30. PMID: 29713760. 3. Koltun ES, Tsuhako AL, Brown DS, Aay N, Arcalas A, Chan V, Du H, Engst S, Ferguson K, Franzini M, Galan A, Holst CR, Huang P, Kane B, Kim MH, Li J, Markby D, Mohan M, Noson K, Plonowski A, Richards SJ, Robertson S, Shaw K, Stott G, Stout TJ, Young J, Yu P, Zaharia CA, Zhang W, Zhou P, Nuss JM, Xu W, Kearney PC. Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31. doi: 10.1016/j.bmcl.2012.04.024. Epub 2012 Apr 16. Erratum in: Bioorg Med Chem Lett. 2012 Aug 1;22(15):5157. PMID: 22560567.
In vitro protocol:
1. Wienert B, Nguyen DN, Guenther A, Feng SJ, Locke MN, Wyman SK, Shin J, Kazane KR, Gregory GL, Carter MAM, Wright F, Conklin BR, Marson A, Richardson CD, Corn JE. Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair. Nat Commun. 2020 Apr 30;11(1):2109. doi: 10.1038/s41467-020-15845-1. PMID: 32355159; PMCID: PMC7193628. 2. Jin S, Ma H, Yang W, Ju H, Wang L, Zhang Z. Cell division cycle 7 is a potential therapeutic target in oral squamous cell carcinoma and is regulated by E2F1. J Mol Med (Berl). 2018 Jun;96(6):513-525. doi: 10.1007/s00109-018-1636-7. Epub 2018 Apr 30. PMID: 29713760.
In vivo protocol:
1. Koltun ES, Tsuhako AL, Brown DS, Aay N, Arcalas A, Chan V, Du H, Engst S, Ferguson K, Franzini M, Galan A, Holst CR, Huang P, Kane B, Kim MH, Li J, Markby D, Mohan M, Noson K, Plonowski A, Richards SJ, Robertson S, Shaw K, Stott G, Stout TJ, Young J, Yu P, Zaharia CA, Zhang W, Zhou P, Nuss JM, Xu W, Kearney PC. Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31. doi: 10.1016/j.bmcl.2012.04.024. Epub 2012 Apr 16. Erratum in: Bioorg Med Chem Lett. 2012 Aug 1;22(15):5157. PMID: 22560567.
1: Koltun ES, Tsuhako AL, Brown DS, Aay N, Arcalas A, Chan V, Du H, Engst S, Ferguson K, Franzini M, Galan A, Holst CR, Huang P, Kane B, Kim MH, Li J, Markby  D, Mohan M, Noson K, Plonowski A, Richards SJ, Robertson S, Shaw K, Stott G, Stout TJ, Young J, Yu P, Zaharia CA, Zhang W, Zhou P, Nuss JM, Xu W, Kearney PC.  Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg Med Chem Lett.  2012 Jun 1;22(11):3727-31. doi: 10.1016/j.bmcl.2012.04.024. Epub 2012 Apr 16. Erratum in: Bioorg Med Chem Lett. 2012 Aug 1;22(15):5157. PubMed PMID: 22560567.

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