CWHM12 | CWHM-12 | CAS#1564286-55-0 | integrin inhibitor

MedKoo Cat#: 526883 | Name: CWHM12

Description:

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

CWHM12 is a α(v) integrin inhibitor. CWHM 12 can suppress all 5 alpha V integrins. CWHM12 not only worked the same way to prevent fibrosis as the genetic deletion method, it also prevent the progression of existing fibrosis in the liver and lungs and reversed some of the damage caused by fibrosis to those organs. Delivering CWHM 12 or a similar small molecule directly into the lungs as an inhalant might offer a way to treat lung fibrosis. harmacological blockade of α(v)-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner.

Chemical Structure

CWHM12

CAS#1564286-55-0

Theoretical Analysis

MedKoo Cat#: 526883

Name: CWHM12

CAS#: 1564286-55-0

Chemical Formula: C26H32BrN5O6

Exact Mass: 589.1536

Molecular Weight: 590.48

Elemental Analysis: C, 52.89; H, 5.46; Br, 13.53; N, 11.86; O, 16.26

Price and Availability

Size	Price	Availability
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 1,350.00	Ready to Ship
500mg	USD 2,850.00	Ready to ship

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Related CAS #

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Synonym

CWHM12; CWHM 12; CWHM-12.

IUPAC/Chemical Name

(3S)-3-(3-bromo-5-(tert-butyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid

InChi Key

YDHAGPCZRFQPOI-NRFANRHFSA-N

InChi Code

InChI=1S/C26H32BrN5O6/c1-26(2,3)16-4-14(5-17(27)8-16)21(10-23(36)37)32-22(35)13-28-24(38)15-6-18(9-19(33)7-15)31-25-29-11-20(34)12-30-25/h4-9,20-21,33-34H,10-13H2,1-3H3,(H,28,38)(H,32,35)(H,36,37)(H2,29,30,31)/t21-/m0/s1

SMILES Code

OC1=CC(C(NCC(N[C@@H](CC(O)=O)C2=CC(Br)=CC(C(C)(C)C)=C2)=O)=O)=CC(NC3=NCC(O)CN3)=C1

Appearance

White to off-white 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

>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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC61215

QC Data

View QC data: current batch, Lot#BBC61215

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

CWHM-12 is a potent inhibitor of αV integrins with IC50s of 0.2, 0.8, 1.5, and 1.8 nM for αvβ8, αvβ3, αvβ6, and αvβ1.

In vitro activity:

To investigate whether the antifibrotic mechanism of CWHM-12 involves inhibition of TGFB activation specifically by PSCs, an in vitro system was developed to study TGFB activation in PSCs. The effects of the integrin antagonist compound CWHM-12 were then evaluated on TGFB activation. It was found that CWHM-12 potently blocked TGFB activation by the PSC cell line with a mean IC50 value of approximately 1.5 nmol/L (SD, 0.78; average, 4 independent experiments). A representative inhibition curve is shown in Figure 9B. In contrast, the negative control enantiomer CWHM-96 had no effect on inhibition of TGF-β activation by the PSCs in this assay, even at 1000-fold higher concentrations (data not shown). A separate study showed that protein expression of the downstream TGFB target α-SMA, also a marker of PSC activation, was reduced in cell culture by incubation with CWHM-12 for 48 hours (Figure 9C and D). MMP activity measured in cell lysates also was reduced (Figure 9E and F). This finding strongly supports a mechanism of TGFB activation by PSC-expressed RGD-binding integrins as a major mediator of pancreatic fibrogenesis. Reference: Cell Mol Gastroenterol Hepatol. 2016 Jul; 2(4): 499–518. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042566/

In vivo activity:

To assess if administration of CWHM-12 still could have an effect after fibrosis already is present (therapeutic mode), minipumps were implanted with CWHM-12 in C57BL/6 female mice on day 5 of cerulein treatment, a time point when some fibrosis already has been established (Figure 6A), and then assessed subsequent changes in fibrosis in the pancreas on day 8. Therapeutic CWHM-12 administration showed effective reduction of collagen accumulation induced by repetitive cerulein treatment by day 8 as assessed by Sirius red staining whereas treatment with CWHM-96 did not (Figure 6A). Results were quantified and confirmed by morphometric analysis (Figure 6B). Consistent with the histologic findings, administration of CWHM-12 also significantly reduced cerulein-induced pancreatic Col1a1 mRNA expression in the therapeutic mode. Treatment with the inactive control compound CWHM-96 had no significant effect (Figure 6C). To evaluate if the decrease in collagen accumulation was associated with decreased PSC activation, the expression of the activated PSC marker α-SMA was analyzed in the treatment groups by immunohistochemistry and by real-time reverse-transcription PCR (Figure 6D and 6E). CWHM-12 treatment resulted in the nearly complete disappearance of activated PSCs. Small-molecule antagonists of this interaction might be developed for treatment of pancreatic fibrotic diseases. Reference: Cell Mol Gastroenterol Hepatol. 2016 Jul; 2(4): 499–518. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042566/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	84.68

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 590.48 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. Henderson NC, Arnold TD, Katamura Y, Giacomini MM, Rodriguez JD, McCarty JH, Pellicoro A, Raschperger E, Betsholtz C, Ruminski PG, Griggs DW, Prinsen MJ, Maher JJ, Iredale JP, Lacy-Hulbert A, Adams RH, Sheppard D. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013 Dec;19(12):1617-24. doi: 10.1038/nm.3282. Epub 2013 Nov 10. PMID: 24216753; PMCID: PMC3855865. 2. Ulmasov B, Neuschwander-Tetri BA, Lai J, Monastyrskiy V, Bhat T, Yates MP, Oliva J, Prinsen MJ, Ruminski PG, Griggs DW. Inhibitors of Arg-Gly-Asp-Binding Integrins Reduce Development of Pancreatic Fibrosis in Mice. Cell Mol Gastroenterol Hepatol. 2016 Mar 16;2(4):499-518. doi: 10.1016/j.jcmgh.2016.03.004. PMID: 28174730; PMCID: PMC5042566.

In vitro protocol:

In vivo protocol:

1: Henderson NC, Arnold TD, Katamura Y, Giacomini MM, Rodriguez JD, McCarty JH, Pellicoro A, Raschperger E, Betsholtz C, Ruminski PG, Griggs DW, Prinsen MJ, Maher JJ, Iredale JP, Lacy-Hulbert A, Adams RH, Sheppard D. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013 Dec;19(12):1617-24. doi: 10.1038/nm.3282. Epub 2013 Nov 10. PubMed PMID: 24216753; PubMed Central PMCID: PMC3855865.