RRD-251 HCl | CAS# 72214-67-6 | Rb-Raf-1 inhibitor

MedKoo Cat#: 574502 | Name: RRD-251 HCl

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Description:

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

RRD-251 is a retinoblastoma tumor suppressor protein (Rb)-Raf-1 interaction inhibitor with potent anti-proliferative, anti-angiogenic and anti-tumor activities.

Chemical Structure

RRD-251 HCl

CAS#72214-67-6

Theoretical Analysis

MedKoo Cat#: 574502

Name: RRD-251 HCl

CAS#: 72214-67-6

Chemical Formula: C8H9Cl3N2S

Exact Mass: 0.0000

Molecular Weight: 271.58

Elemental Analysis: C, 35.38; H, 3.34; Cl, 39.16; N, 10.32; S, 11.80

Price and Availability

Size	Price	Availability	Quantity
25mg	USD 500.00	2 Weeks

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Synonym

RRD-251 hydrochloride, RRD-251 HCl, RRD251 HCl, RRD 251 HCl

IUPAC/Chemical Name

S-(2,4-Dichlorobenzyl)-isothiouronium chloride

InChi Key

COMNQRICZGJVLE-UHFFFAOYSA-N

InChi Code

InChI=1S/C8H8Cl2N2S.ClH/c9-6-2-1-5(7(10)3-6)4-13-8(11)12;/h1-3H,4H2,(H3,11,12);1H

SMILES Code

[NH2+]=C(N)SCC1=CC=C(Cl)C=C1Cl.[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

2934.99.9001

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

RRD-251 HCl is a cell-permeable and orally active isothiouronium compound that potently and selectively disrupts the Rb/Raf-1 interaction while exhibiting no effect against Rb/B-Raf, Rb/E2F1, Rb/prohibitin, Rb/cyclin E, Rb/HDAC1, Raf-1/MEK1, or Raf-1/MEK2 interaction. RRD-251 hydrochloride suppresses cellular E2F transcription activity and reduces serum-induced Rb phosphorylation.

In vitro activity:

RRD-251 enhances all-trans-retinoic acid-induced leukemic cell differentiation. RRD-251 increases the RARE-driven CD38 expression per cell. The RA/c-Raf/GSK-3/RARα axis emerges as a novel differentiation regulatory mechanism susceptible to RRD-251, suggesting enhancing RA-effects with RRD-251 in therapy. Reference: Oncotarget. 2016 Jul 19;7(29):46401-46418. https://pubmed.ncbi.nlm.nih.gov/27331409/

In vivo activity:

Tumors from RRD-251-treated animals showed decreased Rb-Raf-1 interaction in vivo. Growth suppressive effects of RRD-251 were associated with induction of apoptosis as well as a G(1) arrest, with an accompanying decrease in S-phase cells. RRD-251 inhibited Rb phosphorylation and downregulated E2F1 protein levels in these cells. Reference: Mol Cancer Ther. 2010 Dec;9(12):3330-41. https://pubmed.ncbi.nlm.nih.gov/21139044/

	Solvent	mg/mL	mM
Solubility
	DMSO	125.0	460.25

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 271.58 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. Wallace AS, Supnick HT, Bunaciu RP, Yen A. RRD-251 enhances all-trans retinoic acid (RA)-induced differentiation of HL-60 myeloblastic leukemia cells. Oncotarget. 2016 Jul 19;7(29):46401-46418. doi: 10.18632/oncotarget.10136. PMID: 27331409; PMCID: PMC5216806. 2. Treviño JG, Verma M, Singh S, Pillai S, Zhang D, Pernazza D, Sebti SM, Lawrence NJ, Centeno BA, Chellappan SP. Selective disruption of rb-raf-1 kinase interaction inhibits pancreatic adenocarcinoma growth irrespective of gemcitabine sensitivity. Mol Cancer Ther. 2013 Dec;12(12):2722-34. doi: 10.1158/1535-7163.MCT-12-0719. Epub 2013 Oct 9. PMID: 24107447; PMCID: PMC3858536. 3. Singh S, Davis R, Alamanda V, Pireddu R, Pernazza D, Sebti S, Lawrence N, Chellappan S. Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in metastatic melanoma cells and synergizes with dacarbazine. Mol Cancer Ther. 2010 Dec;9(12):3330-41. doi: 10.1158/1535-7163.MCT-10-0442. Epub 2010 Dec 7. PMID: 21139044; PMCID: PMC3058238. 4. Johnson JL, Pillai S, Pernazza D, Sebti SM, Lawrence NJ, Chellappan SP. Regulation of matrix metalloproteinase genes by E2F transcription factors: Rb-Raf-1 interaction as a novel target for metastatic disease. Cancer Res. 2012 Jan 15;72(2):516-26. doi: 10.1158/0008-5472.CAN-11-2647. Epub 2011 Nov 15. Erratum in: Cancer Res. 2012 Mar 1;72(5):1317. PMID: 22086850; PMCID: PMC3261351.

In vitro protocol:

In vivo protocol:

1. Singh S, Davis R, Alamanda V, Pireddu R, Pernazza D, Sebti S, Lawrence N, Chellappan S. Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in metastatic melanoma cells and synergizes with dacarbazine. Mol Cancer Ther. 2010 Dec;9(12):3330-41. doi: 10.1158/1535-7163.MCT-10-0442. Epub 2010 Dec 7. PMID: 21139044; PMCID: PMC3058238. 2. Johnson JL, Pillai S, Pernazza D, Sebti SM, Lawrence NJ, Chellappan SP. Regulation of matrix metalloproteinase genes by E2F transcription factors: Rb-Raf-1 interaction as a novel target for metastatic disease. Cancer Res. 2012 Jan 15;72(2):516-26. doi: 10.1158/0008-5472.CAN-11-2647. Epub 2011 Nov 15. Erratum in: Cancer Res. 2012 Mar 1;72(5):1317. PMID: 22086850; PMCID: PMC3261351.

1: Supnick HT, Bunaciu RP, Yen A. The c-Raf modulator RRD-251 enhances nuclear c-Raf/GSK-3/VDR axis signaling and augments 1,25-dihydroxyvitamin D3-induced differentiation of HL-60 myeloblastic leukemia cells. Oncotarget. 2018 Jan 19;9(11):9808-9824. doi: 10.18632/oncotarget.24275. PMID: 29515772; PMCID: PMC5839403. 2: Wallace AS, Supnick HT, Bunaciu RP, Yen A. RRD-251 enhances all-trans retinoic acid (RA)-induced differentiation of HL-60 myeloblastic leukemia cells. Oncotarget. 2016 Jul 19;7(29):46401-46418. doi: 10.18632/oncotarget.10136. PMID: 27331409; PMCID: PMC5216806. 3: Wu J, Sun S, Li W, Chen Y, Li H. pRb phosphorylation regulates the proliferation of supporting cells in gentamicin-damaged neonatal avian utricle. Neuroreport. 2014 Oct 1;25(14):1144-50. doi: 10.1097/WNR.0000000000000241. PMID: 25100553. 4: Treviño JG, Verma M, Singh S, Pillai S, Zhang D, Pernazza D, Sebti SM, Lawrence NJ, Centeno BA, Chellappan SP. Selective disruption of rb-raf-1 kinase interaction inhibits pancreatic adenocarcinoma growth irrespective of gemcitabine sensitivity. Mol Cancer Ther. 2013 Dec;12(12):2722-34. doi: 10.1158/1535-7163.MCT-12-0719. Epub 2013 Oct 9. PMID: 24107447; PMCID: PMC3858536. 5: Alamanda V, Singh S, Lawrence NJ, Chellappan SP. Nicotine-mediated induction of E-selectin in aortic endothelial cells requires Src kinase and E2F1 transcriptional activity. Biochem Biophys Res Commun. 2012 Feb 3;418(1):56-61. doi: 10.1016/j.bbrc.2011.12.127. Epub 2012 Jan 3. PMID: 22240023; PMCID: PMC3273677. 6: Davis R, Pillai S, Lawrence N, Sebti S, Chellappan SP. TNF-α-mediated proliferation of vascular smooth muscle cells involves Raf-1-mediated inactivation of Rb and transcription of E2F1-regulated genes. Cell Cycle. 2012 Jan 1;11(1):109-18. doi: 10.4161/cc.11.1.18473. Epub 2012 Jan 1. PMID: 22185776; PMCID: PMC3272234. 7: Johnson JL, Pillai S, Pernazza D, Sebti SM, Lawrence NJ, Chellappan SP. Regulation of matrix metalloproteinase genes by E2F transcription factors: Rb- Raf-1 interaction as a novel target for metastatic disease. Cancer Res. 2012 Jan 15;72(2):516-26. doi: 10.1158/0008-5472.CAN-11-2647. Epub 2011 Nov 15. Erratum in: Cancer Res. 2012 Mar 1;72(5):1317. PMID: 22086850; PMCID: PMC3261351. 8: Singh S, Davis R, Alamanda V, Pireddu R, Pernazza D, Sebti S, Lawrence N, Chellappan S. Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in metastatic melanoma cells and synergizes with dacarbazine. Mol Cancer Ther. 2010 Dec;9(12):3330-41. doi: 10.1158/1535-7163.MCT-10-0442. Epub 2010 Dec 7. PMID: 21139044; PMCID: PMC3058238. 9: Davis RK, Chellappan S. Disrupting the Rb-Raf-1 interaction: a potential therapeutic target for cancer. Drug News Perspect. 2008 Jul-Aug;21(6):331-5. doi: 10.1358/dnp.2008.21.6.1246832. PMID: 18836591; PMCID: PMC2800199. 10: Kinkade R, Dasgupta P, Carie A, Pernazza D, Carless M, Pillai S, Lawrence N, Sebti SM, Chellappan S. A small molecule disruptor of Rb/Raf-1 interaction inhibits cell proliferation, angiogenesis, and growth of human tumor xenografts in nude mice. Cancer Res. 2008 May 15;68(10):3810-8. doi: 10.1158/0008-5472.CAN-07-6672. PMID: 18483265; PMCID: PMC3233839.

View History

IDX-989

MedKoo CAT#: 576586

CAS#: 881924-55-6