Home >> Research Area >>Metabolism>>KRAS-PDEδ>> Deltarasin hydrochloride

Deltarasin hydrochloride

inhibitor of KRAS-PDEδ interaction, potent and selective CAS# 1440898-82-7

Deltarasin hydrochloride

Catalog No. BCC4270----Order now to get a substantial discount!

Product Name & Size Price Stock
Deltarasin hydrochloride: 5mg $173 In Stock
Deltarasin hydrochloride: 10mg Please Inquire In Stock
Deltarasin hydrochloride: 20mg Please Inquire Please Inquire
Deltarasin hydrochloride: 50mg Please Inquire Please Inquire
Deltarasin hydrochloride: 100mg Please Inquire Please Inquire
Deltarasin hydrochloride: 200mg Please Inquire Please Inquire
Deltarasin hydrochloride: 500mg Please Inquire Please Inquire
Deltarasin hydrochloride: 1000mg Please Inquire Please Inquire
Related Products
  • Deltarasin

    Catalog No.:BCC1524
    CAS No.:1440898-61-2

Quality Control of Deltarasin hydrochloride

Number of papers citing our products

Chemical structure

Deltarasin hydrochloride

3D structure

Chemical Properties of Deltarasin hydrochloride

Cas No. 1440898-82-7 SDF Download SDF
PubChem ID 91826089 Appearance Powder
Formula C40H38ClN5O M.Wt 640.22
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 100 mM in water and to 100 mM in DMSO
Chemical Name 1-benzyl-2-[4-[(2S)-2-(2-phenylbenzimidazol-1-yl)-2-piperidin-4-ylethoxy]phenyl]benzimidazole;trihydrochloride
SMILES C1CNCCC1C(COC2=CC=C(C=C2)C3=NC4=CC=CC=C4N3CC5=CC=CC=C5)N6C7=CC=CC=C7N=C6C8=CC=CC=C8.Cl.Cl.Cl
Standard InChIKey NCIOVAYUMQEQEU-VKZSUDIWSA-N
Standard InChI InChI=1S/C40H37N5O.3ClH/c1-3-11-29(12-4-1)27-44-36-17-9-7-15-34(36)42-39(44)32-19-21-33(22-20-32)46-28-38(30-23-25-41-26-24-30)45-37-18-10-8-16-35(37)43-40(45)31-13-5-2-6-14-31;;;/h1-22,30,38,41H,23-28H2;3*1H/t38-;;;/m1.../s1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of Deltarasin hydrochloride

DescriptionHigh affinity PDEδ-KRAS interaction inhibitor (Kd = 41 nM); binds to PDEδ. Reduces proliferation and induces cell death of KRAS-dependent Panc-Tu-1 and Capan-1 pancreatic cancer cells. Attenuates tumor growth of Panc-Tu-1 xenografts in mice.

Deltarasin hydrochloride Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

Deltarasin hydrochloride Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of Deltarasin hydrochloride

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 1.562 mL 7.8098 mL 15.6196 mL 31.2393 mL 39.0491 mL
5 mM 0.3124 mL 1.562 mL 3.1239 mL 6.2479 mL 7.8098 mL
10 mM 0.1562 mL 0.781 mL 1.562 mL 3.1239 mL 3.9049 mL
50 mM 0.0312 mL 0.1562 mL 0.3124 mL 0.6248 mL 0.781 mL
100 mM 0.0156 mL 0.0781 mL 0.1562 mL 0.3124 mL 0.3905 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on Deltarasin hydrochloride

Deltarasin hydrochloride is a selective inhibitor of KRAS-PDEδ interaction with IC50 value of 41±12 nM [1].

KRAS, also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, is a protein and works as a molecular on/off switch whose mutant is an essential step in the development of many cancers. PDEδ (prenyl binding protein) controls the spatial organization of K-Ras, which enhances Ras diffusion in the cytosol. Inhibition of the Ras-PDEδ interaction by small molecules impairs Ras localization and signaling has becoming a promising strategy to treat cancers in clinic [1, 2].

Deltarasin hydrochloride is a potent KRAS-PDEδ interaction inhibitor. When tested with human pancreatic ductal adenocarcinoma cells Deltarasin hydrochloride showed inhibition on KRAS-PDEδ interaction to inhibit oncogenic RAS signaling and suppressed cell proliferation by binding to PDEδ with Kd value of 41 nM [1].

In nude mice model with Panc-Tu-I xenograft, administration of Deltarasin hydrochloride (10, 15 mg/kg) impaired cells growth and decreased tumor volume after 9 days in a dose-dependent manner [1].

References:
[1].  Zimmermann, G., et al., Small molecule inhibition of the KRAS-PDEdelta interaction impairs oncogenic KRAS signalling. Nature, 2013. 497(7451): p. 638-42.
[2].  The KRAS-PDEdelta interaction is a therapeutic target. Cancer Discov, 2013. 3(7): p. Of20.

Featured Products
New Products
 

References on Deltarasin hydrochloride

Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Intravenous Palonosetron Hydrochloride.[Pubmed:28346200]

Int J Pharm Compd. 2017 Jan-Feb;21(1):76-82.

Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 RA, and dexamethasone combination therapy is standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein we describe the physical and chemical stability of rolapitant injectable emulsion 166.5 mg in 92.5 mL (185 mg hydrochloride salt) admixed with palonosetron injection 0.25 mg in 5 mL (0.28 mg hydrochloride salt). Admixtures were prepared and stored in two types of container closures (110-mL Crystal Zenith plastic and glass bottles) and four types of intravenous administration sets (or intravenous tubing sets). Assessment of the physical and chemical stability was conducted on the admixtures in the ready-to-use container closure systems as supplied by the manufacturer, stored at room temperature (20 degrees C to 25 degrees C under fluorescent light), and evaluated at 0, 1, and 6 hours; 1 and 2 days; and under refrigeration (2 degrees C to 8 degrees C protected from light) after 1, 3, and 7 days. For admixtures in intravenous tubing sets, the assessment of physicochemical stability was performed after 0 and 7 hours of storage at 20 degrees C to 25 degrees C initially, and then after 20 hours (total 27 hours) at 2 degrees C to 8 degrees C protected from light. Physical stability was assessed by visual examination of the container contents under normal room light, and measuring turbidity and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations and impurity levels with high-performance liquid chromatographic analysis. The results indicated that all samples were physically compatible throughout the duration of the study. The pH, turbidity, and particulate matter of the admixture stayed within narrow and acceptable ranges. Rolapitant admixed with palonosetron was chemically stable when admixed in glass and Crystal Zenith bottles for at least 48 hours at room temperature and for 7 days under refrigeration, as well as in the four selected intravenous tubing sets for 7 hours at 20 degrees C to 25 degrees C and then for 20 hours at 2 degrees C to 8 degrees C. No loss of potency of any admixed components occurred in the samples stored at the two temperature ranges and time period studied.

[The Discovery, Research and Development of Etelcalcetide Hydrochloride, the World 1st Intravenous Calcimimetics.][Pubmed:28336830]

Clin Calcium. 2017;27(4):537-545.

Etelcalcetide hydrochloride is the first intravenous calcimimetics agent for secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is to be administered through dialysis circuit by physician or medical staff upon completion of dialysis and such administration is expected to reduce the burden of medication in patients. From the nonclinical study results, etelcalcetide functions as an allosteric activator of calcium-sensing receptor(CaSR). Etelcalcetide suppressed PTH secretion both in vitro and in vivo. In a rat model of chronic renal insufficiency, etelcalcetide suppressed SHPT disorders, such as parathyroid gland hypertrophy, bone disorder, and ectopic calcification. In conclusion, etelcalcetide hydrochloride is expected to exhibit therapeutic effect against each SHPT condition by decreasing blood PTH concentrations via CaSR-agonist activity in the clinical situation.

Study on the interaction of 6-(2-morpholin-4-yl-ethyl)-6H-indolo [2,3-b]quinoxaline hydrochloride with human serum albumin by fluorescence spectroscopy.[Pubmed:28355158]

Methods Appl Fluoresc. 2016 Sep 14;4(3):034012.

Under physiological conditions, in vitro interaction between the bio-active substance 6-(2-morpholin-4-yl-ethyl)-6H-indolo[2,3-b]quinoxaline hydrochloride (MIQ) and human serum albumin (HSA) was investigated at an excitation wavelength 260 nm and at different temperatures (298 K, 308 K and 313 K) by fluorescence emission spectroscopy. From spectral analysis, MIQ showed a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The binding constant is estimated asK A = 2.55 x 10(-4) l . mol(-1) at 298 K. Based on the thermodynamic parameters evaluated from the van 't Hoff equation, the enthalpy change (DeltaH degrees ) and entropy change (DeltaS degrees ) were derived to be negative values. A value of 2.37 nm for the average distance r between MIQ (acceptor) and tryptophan residues of HSA (donor) was derived from the fluorescence resonance energy transfer. UV/vis absorption spectra were used to confirm the quenching mechanism.

Identification of pyrolysis products of the new psychoactive substance 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) and its iodo analogue bk-2C-I.[Pubmed:28371351]

Drug Test Anal. 2018 Jan;10(1):229-236.

2-Amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) has recently emerged as a new psychoactive substance (NPS). It is most commonly consumed orally, although there are indications that it might also be ingested by inhalation or 'smoking'. Information about the stability of bk-2C-B when exposed to heat is unavailable and the potential for pyrolytic degradation and formation of unknown substances available for inhalation prompted an investigation using a simulated 'meth pipe' scenario. Twelve products following pyrolysis of bk-2C-B were detected and verified by organic synthesis of the corresponding standards. In addition, 2-amino-1-(4-iodo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-I) was characterized for the first time and subjected to pyrolysis as well. Similar products were formed, which indicated that the replacement of the bromo with the iodo substituent did not affect the pyrolysis pattern under the conditions used. Two additional products were detected in the bk-2C-I pyrolates, namely 1-(2,5-dimethoxyphenyl)-ethanone and 1-iodo-4-ethenyl-5-methoxyphenol. The potential ingestion of pyrolysis products with unknown toxicity adds an element of concern. Copyright (c) 2017 John Wiley & Sons, Ltd.

Structure guided design and kinetic analysis of highly potent benzimidazole inhibitors targeting the PDEdelta prenyl binding site.[Pubmed:24884780]

J Med Chem. 2014 Jun 26;57(12):5435-48.

K-Ras is one of the most frequently mutated signal transducing human oncogenes. Ras signaling activity requires correct cellular localization of the GTPase. The spatial organization of K-Ras is controlled by the prenyl binding protein PDEdelta, which enhances Ras diffusion in the cytosol. Inhibition of the Ras-PDEdelta interaction by small molecules impairs Ras localization and signaling. Here we describe in detail the identification and structure guided development of Ras-PDEdelta inhibitors targeting the farnesyl binding pocket of PDEdelta with nanomolar affinity. We report kinetic data that characterize the binding of the most potent small molecule ligands to PDEdelta and prove their binding to endogenous PDEdelta in cell lysates. The PDEdelta inhibitors provide promising starting points for the establishment of new drug discovery programs aimed at cancers harboring oncogenic K-Ras.

Small molecule inhibition of the KRAS-PDEdelta interaction impairs oncogenic KRAS signalling.[Pubmed:23698361]

Nature. 2013 May 30;497(7451):638-42.

The KRAS oncogene product is considered a major target in anticancer drug discovery. However, direct interference with KRAS signalling has not yet led to clinically useful drugs. Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEdelta, which sustains the spatial organization of KRAS by facilitating its diffusion in the cytoplasm. Here we report that interfering with binding of mammalian PDEdelta to KRAS by means of small molecules provides a novel opportunity to suppress oncogenic RAS signalling by altering its localization to endomembranes. Biochemical screening and subsequent structure-based hit optimization yielded inhibitors of the KRAS-PDEdelta interaction that selectively bind to the prenyl-binding pocket of PDEdelta with nanomolar affinity, inhibit oncogenic RAS signalling and suppress in vitro and in vivo proliferation of human pancreatic ductal adenocarcinoma cells that are dependent on oncogenic KRAS. Our findings may inspire novel drug discovery efforts aimed at the development of drugs targeting oncogenic RAS.

Keywords:

Deltarasin hydrochloride,1440898-82-7,Natural Products,KRAS-PDEδ, buy Deltarasin hydrochloride , Deltarasin hydrochloride supplier , purchase Deltarasin hydrochloride , Deltarasin hydrochloride cost , Deltarasin hydrochloride manufacturer , order Deltarasin hydrochloride , high purity Deltarasin hydrochloride

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: