iP300w | CAS#1889284-33-6 | p300/CBP inhibitor

MedKoo Cat#: 462500 | Name: iP300w

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Description:

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

iP300w is a potent p300/CBP inhibitor. IP300w efficiently suppresses CIC-DUX4 transcriptional activity and reverses CIC-DUX4 induced acetylation. iP300w is active at 100-fold lower concentrations than related stereoisomers or A-485. At low doses, iP300w shows specificity to CDS cancer cell lines, rapidly inducing cell cycle arrest and preventing growth of established CDS xenograft tumors when delivered in vivo. The effectiveness of iP300w to inactivate CIC-DUX4 highlights a promising therapeutic opportunity for CDS.

Chemical Structure

iP300w

CAS#1889284-33-6

Theoretical Analysis

MedKoo Cat#: 462500

Name: iP300w

CAS#: 1889284-33-6

Chemical Formula: C29H27F5N6O4

Exact Mass: 618.2014

Molecular Weight: 618.57

Elemental Analysis: C, 56.31; H, 4.40; F, 15.36; N, 13.59; O, 10.35

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 650.00	2 Weeks

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Synonym

iP300w; iP-300w; iP 300w;

IUPAC/Chemical Name

2-[3'-Fluoro-5'-[1-[2-(methylamino)-2-oxoethyl]-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro(imidazolidine-4,1'-inden)-1-yl]-N-(4-fluorobenzyl)-N-(1,1,1-trifluoropropane-2-yl)acetamide

InChi Key

SWXCHCQCWFXILM-UHFFFAOYSA-N

InChi Code

InChI=1S/C29H27F5N6O4/c1-16(29(32,33)34)39(12-17-3-6-20(30)7-4-17)25(42)15-40-26(43)28(37-27(40)44)10-23(31)21-9-18(5-8-22(21)28)19-11-36-38(13-19)14-24(41)35-2/h3-9,11,13,16,23H,10,12,14-15H2,1-2H3,(H,35,41)(H,37,44)

SMILES Code

O=C(NC)CN(N=C1)C=C1C(C=C2)=CC3=C2C(N4)(CC3F)C(N(CC(N(CC5=CC=C(F)C=C5)C(C)C(F)(F)F)=O)C4=O)=O

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

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

P300/CBP-IN-5 is a potent p300/CBP histone acetyltransferase inhibitor that has an IC50 of 18.8 nM.

In vitro activity:

This study describes the activity of a new spirocyclic EP300/CBP inhibitor, iP300w, which inhibits the cytotoxicity of the DUX4 protein and reverses the overexpression of most DUX4 target genes, in engineered cell lines and FSHD myoblasts, as well as in an FSHD animal model. Reference: Sci Adv. 2019 Sep 11;5(9):eaaw7781. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739093/

In vivo activity:

When tumors were palpable (day 9) iP300w injections (1.4 mg/kg b.i.d.) were initiated and the progression of tumor growth was monitored. While tumor growth was evident in the control mice, growth was halted (5/8) or significantly diminished (3/8) in the treated mice (Fig. 4I, J). Reference: Oncogenesis. 2021 Oct 12;10(10):68. https://pubmed.ncbi.nlm.nih.gov/34642317/

	Solvent	mg/mL	mM
Solubility
	DMSO	61.9	100.00

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 618.57 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. Bosnakovski D, Ener ET, Cooper MS, Gearhart MD, Knights KA, Xu NC, Palumbo CA, Toso EA, Marsh GP, Maple HJ, Kyba M. Inactivation of the CIC-DUX4 oncogene through P300/CBP inhibition, a therapeutic approach for CIC-DUX4 sarcoma. Oncogenesis. 2021 Oct 12;10(10):68. doi: 10.1038/s41389-021-00357-4. PMID: 34642317; PMCID: PMC8511258. 2. Bosnakovski D, da Silva MT, Sunny ST, Ener ET, Toso EA, Yuan C, Cui Z, Walters MA, Jadhav A, Kyba M. A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death. Sci Adv. 2019 Sep 11;5(9):eaaw7781. doi: 10.1126/sciadv.aaw7781. PMID: 31535023; PMCID: PMC6739093.

In vitro protocol:

In vivo protocol:

1: Crawford MC, Tripu DR, Barritt SA, Jing Y, Gallimore D, Kales SC, Bhanu NV, Xiong Y, Fang Y, Butler KAT, LeClair CA, Coussens NP, Simeonov A, Garcia BA, Dibble CC, Meier JL. Comparative Analysis of Drug-like EP300/CREBBP Acetyltransferase Inhibitors. ACS Chem Biol. 2023 Sep 22. doi: 10.1021/acschembio.3c00293. Epub ahead of print. PMID: 37737090. 2: Crawford MC, Tripu DR, Barritt SA, Jing Y, Gallimore D, Kales SC, Bhanu NV, Xiong Y, Fang Y, Butler KAT, LeClair CA, Coussens NP, Simeonov A, Garcia BA, Dibble CC, Meier JL. Comparative analysis of drug-like EP300/CREBBP acetyltransferase inhibitors. bioRxiv [Preprint]. 2023 May 16:2023.05.15.540887. doi: 10.1101/2023.05.15.540887. PMID: 37292747; PMCID: PMC10245587. 3: Bosnakovski D, Ener ET, Cooper MS, Gearhart MD, Knights KA, Xu NC, Palumbo CA, Toso EA, Marsh GP, Maple HJ, Kyba M. Inactivation of the CIC-DUX4 oncogene through P300/CBP inhibition, a therapeutic approach for CIC-DUX4 sarcoma. Oncogenesis. 2021 Oct 12;10(10):68. doi: 10.1038/s41389-021-00357-4. PMID: 34642317; PMCID: PMC8511258. 4: Bosnakovski D, da Silva MT, Sunny ST, Ener ET, Toso EA, Yuan C, Cui Z, Walters MA, Jadhav A, Kyba M. A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death. Sci Adv. 2019 Sep 11;5(9):eaaw7781. doi: 10.1126/sciadv.aaw7781. PMID: 31535023; PMCID: PMC6739093.