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MedKoo Cat#: 206939 | Name: Deltarasin HCl
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Description:

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

Deltarasin is a high affinity PDEδ-KRAS interaction inhibitor. Deltarasin can inhibit KRAS-PDEδ interactions by binding to a hydrophobic pocket on PDEδ, resulting in the impairment of cell growth, KRAS activity, and RAS/RAF signaling in human pancreatic ductal adenocarcinoma cell lines. The anti-cancer cell activity of deltarasin can be enhanced by simultaneously blocking "tumor protective" autophagy, but inhibited if combined with an anti-oxidant.

Chemical Structure

Deltarasin HCl
Deltarasin HCl
CAS#1440898-82-7 (HCl)

Theoretical Analysis

MedKoo Cat#: 206939

Name: Deltarasin HCl

CAS#: 1440898-82-7 (HCl)

Chemical Formula: C40H40Cl3N5O

Exact Mass: 0.0000

Molecular Weight: 713.14

Elemental Analysis: C, 67.37; H, 5.65; Cl, 14.91; N, 9.82; O, 2.24

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
25mg USD 950.00 2 Weeks
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Related CAS #
1440898-82-7 (HCl) 1440898-61-2 (free base)
Synonym
Deltarasin HCl; Deltarasin hydrochloride; Deltarasin (trihydrochloride); Deltarasin trihydrochloride
IUPAC/Chemical Name
2-[4-[(2S)-2-(2-phenyl-1H-benzimidazol-1-yl)-2-(4-piperidinyl)ethoxy]phenyl]-1-(phenylmethyl)-1H-benzimidazole, trihydrochloride
InChi Key
NCIOVAYUMQEQEU-VKZSUDIWSA-N
InChi Code
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
SMILES Code
[H]Cl.[H]Cl.[H]Cl.C1(C2=CC=C(OC[C@@H](N3C4=CC=CC=C4N=C3C5=CC=CC=C5)C6CCNCC6)C=C2)=NC7=CC=CC=C7N1CC8=CC=CC=C8
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
>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
KRAS is an oncogene product that acts as a GTPase tethered to cell membranes to assist in various cell signaling pathways. The prenyl-binding protein PDEδ regulates the correct localization and signaling of farnesylated KRAS by facilitating its diffusion to the cytoplasm
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Deltarasin is a small molecule that binds to the farnesyl-binding pocket of PDEδ (Kd = 41 nM) in cells thus inhibiting its interaction with KRAS and disrupting RAS signaling.
In vitro activity:
In Fig. 4a, coimmunoprecipitation studies using KRAS antibodies showed that deltarasin treatment reduces the amount of PDEδ in the immunoprecipitate, demonstrating that deltarasin inhibits -PDEδ interactions in the H358 cell line used. A549 cells were next treated with deltarasin and performed the RAS activation assay to measure the level of GTP-RAS. As shown in Fig. 4b, treatment of A549 cells with deltarasin significantly decreases the amount of GTP-RAS observed relative to the control cells. Finally, as shown in Fig. 4c, similar to the results previously reported in pancreatic cancer cells26, treatment of A549 cells and H358 cells with deltarasin also significantly reduces the amount of protein at the PM and displaced KRAS into the EM. In contrast, in the control untreated cells, it was mainly localized at the PM. The above observations demonstrate that deltarasin can inhibit the interaction of KRAS with PDEδ and suppresses the RAS downstream signaling pathways in lung cancer cells. Reference: Cell Death Dis. 2018 Feb; 9(2): 216. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833846/
In vivo activity:
The in vivo efficacy of deltarasin in the context of mutant KRAS was next assessed. A549 cells were injected into nude mice, and the tumors were allowed to grow to about 60 mm3 in size and treated daily with deltarasin for 21 days. Figure 3a shows that deltarasin suppressed tumor growth starting at day 9 and showed significant suppression from day 15 to day 21 when compared to the vehicletreated controls. At the day of harvest, the net tumor mass was determined and the average tumor weight of the deltarasin treatment group was 57% less than the average tumor weight of the control group (Fig. 3b). The mice (n = 5) exhibited no significant body weight loss or apparent toxicity after treatment with deltarasin (Fig. 3c). Taken together, these data demonstrated that deltarasin is effective in suppressing KRAS-driven lung tumor growth. Reference: Cell Death Dis. 2018 Feb; 9(2): 216. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833846/
Solvent mg/mL mM
Solubility
DMSO 30.0 42.07
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 713.14 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. Leung ELH, Luo LX, Liu ZQ, Wong VKW, Lu LL, Xie Y, Zhang N, Qu YQ, Fan XX, Li Y, Huang M, Xiao DK, Huang J, Zhou YL, He JX, Ding J, Yao XJ, Ward DC, Liu L. Inhibition of KRAS-dependent lung cancer cell growth by deltarasin: blockage of autophagy increases its cytotoxicity. Cell Death Dis. 2018 Feb 13;9(2):216. doi: 10.1038/s41419-017-0065-9. PMID: 29440631; PMCID: PMC5833846. 2. Xu H, Zhou S, Xia H, Yu H, Tang Q, Bi F. MEK nuclear localization promotes YAP stability via sequestering β-TrCP in KRAS mutant cancer cells. Cell Death Differ. 2019 Nov;26(11):2400-2415. doi: 10.1038/s41418-019-0309-6. Epub 2019 Mar 4. PMID: 30833665; PMCID: PMC6889282.
In vitro protocol:
1. Leung ELH, Luo LX, Liu ZQ, Wong VKW, Lu LL, Xie Y, Zhang N, Qu YQ, Fan XX, Li Y, Huang M, Xiao DK, Huang J, Zhou YL, He JX, Ding J, Yao XJ, Ward DC, Liu L. Inhibition of KRAS-dependent lung cancer cell growth by deltarasin: blockage of autophagy increases its cytotoxicity. Cell Death Dis. 2018 Feb 13;9(2):216. doi: 10.1038/s41419-017-0065-9. PMID: 29440631; PMCID: PMC5833846. 2. Xu H, Zhou S, Xia H, Yu H, Tang Q, Bi F. MEK nuclear localization promotes YAP stability via sequestering β-TrCP in KRAS mutant cancer cells. Cell Death Differ. 2019 Nov;26(11):2400-2415. doi: 10.1038/s41418-019-0309-6. Epub 2019 Mar 4. PMID: 30833665; PMCID: PMC6889282.
In vivo protocol:
1. Leung ELH, Luo LX, Liu ZQ, Wong VKW, Lu LL, Xie Y, Zhang N, Qu YQ, Fan XX, Li Y, Huang M, Xiao DK, Huang J, Zhou YL, He JX, Ding J, Yao XJ, Ward DC, Liu L. Inhibition of KRAS-dependent lung cancer cell growth by deltarasin: blockage of autophagy increases its cytotoxicity. Cell Death Dis. 2018 Feb 13;9(2):216. doi: 10.1038/s41419-017-0065-9. PMID: 29440631; PMCID: PMC5833846. 2. Xu H, Zhou S, Xia H, Yu H, Tang Q, Bi F. MEK nuclear localization promotes YAP stability via sequestering β-TrCP in KRAS mutant cancer cells. Cell Death Differ. 2019 Nov;26(11):2400-2415. doi: 10.1038/s41418-019-0309-6. Epub 2019 Mar 4. PMID: 30833665; PMCID: PMC6889282.
1: Bello M, Correa-Basurto J, Vargas-Mejía MÁ. Molecular mechanism of the association and dissociation of Deltarasin from the heterodimeric KRas4B-PDEδ complex. Biopolymers. 2019 Nov;110(11):e23333. doi: 10.1002/bip.23333. Epub 2019 Sep 30. PMID: 31568570. 2: Leung ELH, Luo LX, Liu ZQ, Wong VKW, Lu LL, Xie Y, Zhang N, Qu YQ, Fan XX, Li Y, Huang M, Xiao DK, Huang J, Zhou YL, He JX, Ding J, Yao XJ, Ward DC, Liu L. Inhibition of KRAS-dependent lung cancer cell growth by deltarasin: blockage of autophagy increases its cytotoxicity. Cell Death Dis. 2018 Feb 13;9(2):216. doi: 10.1038/s41419-017-0065-9. PMID: 29440631; PMCID: PMC5833846. 3: Arendt KAM, Ntaliarda G, Armenis V, Kati D, Henning C, Giotopoulou GA, Pepe MAA, Klotz LV, Lamort AS, Hatz RA, Kobold S, Schamberger AC, Stathopoulos GT. An In Vivo Inflammatory Loop Potentiates KRAS Blockade. Biomedicines. 2022 Mar 3;10(3):592. doi: 10.3390/biomedicines10030592. PMID: 35327394; PMCID: PMC8945202. 4: Papke B, Murarka S, Vogel HA, Martín-Gago P, Kovacevic M, Truxius DC, Fansa EK, Ismail S, Zimmermann G, Heinelt K, Schultz-Fademrecht C, Al Saabi A, Baumann M, Nussbaumer P, Wittinghofer A, Waldmann H, Bastiaens PI. Identification of pyrazolopyridazinones as PDEδ inhibitors. Nat Commun. 2016 Apr 20;7:11360. doi: 10.1038/ncomms11360. PMID: 27094677; PMCID: PMC4843002. 5: Agalioti T, Giannou AD, Krontira AC, Kanellakis NI, Kati D, Vreka M, Pepe M, Spella M, Lilis I, Zazara DE, Nikolouli E, Spiropoulou N, Papadakis A, Papadia K, Voulgaridis A, Harokopos V, Stamou P, Meiners S, Eickelberg O, Snyder LA, Antimisiaris SG, Kardamakis D, Psallidas I, Marazioti A, Stathopoulos GT. Mutant KRAS promotes malignant pleural effusion formation. Nat Commun. 2017 May 16;8:15205. doi: 10.1038/ncomms15205. PMID: 28508873; PMCID: PMC5440809. 6: Lee J, Lee HJ, Lee Y, Lim B, Gam J, Oh DC, Lee J. Development of PD3 and PD3-B for PDEδ inhibition to modulate KRAS activity. J Enzyme Inhib Med Chem. 2022 Dec;37(1):1656-1666. doi: 10.1080/14756366.2022.2086865. PMID: 35695156; PMCID: PMC9225715. 7: Xu H, Zhou S, Xia H, Yu H, Tang Q, Bi F. MEK nuclear localization promotes YAP stability via sequestering β-TrCP in KRAS mutant cancer cells. Cell Death Differ. 2019 Nov;26(11):2400-2415. doi: 10.1038/s41418-019-0309-6. Epub 2019 Mar 4. PMID: 30833665; PMCID: PMC6889282. 8: O'Bryan JP. Pharmacological targeting of RAS: Recent success with direct inhibitors. Pharmacol Res. 2019 Jan;139:503-511. doi: 10.1016/j.phrs.2018.10.021. Epub 2018 Oct 23. PMID: 30366101; PMCID: PMC6360110. 9: Zhong H, Zhang YJ, Shan XB. Exploring binding modes of the selected inhibitors to phosphodiesterase delta by all-atom molecular dynamics simulations and free energy calculations. J Biomol Struct Dyn. 2019 Jun;37(9):2415-2429. doi: 10.1080/07391102.2018.1491417. Epub 2019 Jan 10. PMID: 30052144. 10: Dietrich P, Koch A, Fritz V, Hartmann A, Bosserhoff AK, Hellerbrand C. Wild type Kirsten rat sarcoma is a novel microRNA-622-regulated therapeutic target for hepatocellular carcinoma and contributes to sorafenib resistance. Gut. 2018 Jul;67(7):1328-1341. doi: 10.1136/gutjnl-2017-315402. Epub 2017 Dec 23. PMID: 29275358. 11: Zhang X, Cao S, Barila G, Edreira MM, Hong K, Wankhede M, Naim N, Buck M, Altschuler DL. Cyclase-associated protein 1 (CAP1) is a prenyl-binding partner of Rap1 GTPase. J Biol Chem. 2018 May 18;293(20):7659-7673. doi: 10.1074/jbc.RA118.001779. Epub 2018 Apr 4. Erratum in: J Biol Chem. 2018 Sep 7;293(36):13849. PMID: 29618512; PMCID: PMC5961064. 12: Tamanoi F, Lu J. Recent progress in developing small molecule inhibitors designed to interfere with ras membrane association: toward inhibiting K-Ras and N-Ras functions. Enzymes. 2013;34 Pt. B:181-200. doi: 10.1016/B978-0-12-420146-0.00008-1. Epub 2013 Nov 7. PMID: 25034105. 13: Gulyás G, Radvánszki G, Matuska R, Balla A, Hunyady L, Balla T, Várnai P. Plasma membrane phosphatidylinositol 4-phosphate and 4,5-bisphosphate determine the distribution and function of K-Ras4B but not H-Ras proteins. J Biol Chem. 2017 Nov 17;292(46):18862-18877. doi: 10.1074/jbc.M117.806679. Epub 2017 Sep 22. PMID: 28939768; PMCID: PMC5704471. 14: Baker NM, Der CJ. Cancer: Drug for an 'undruggable' protein. Nature. 2013 May 30;497(7451):577-8. doi: 10.1038/nature12248. Epub 2013 May 22. PMID: 23698372; PMCID: PMC4902159. 15: Klein CH, Truxius DC, Vogel HA, Harizanova J, Murarka S, Martín-Gago P, Bastiaens PIH. PDEδ inhibition impedes the proliferation and survival of human colorectal cancer cell lines harboring oncogenic KRas. Int J Cancer. 2019 Feb 15;144(4):767-776. doi: 10.1002/ijc.31859. Epub 2018 Dec 4. PMID: 30194764; PMCID: PMC6519276. 16: Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PI, Waldmann H. Small molecule inhibition of the KRAS-PDEδ interaction impairs oncogenic KRAS signalling. Nature. 2013 May 30;497(7451):638-42. doi: 10.1038/nature12205. Epub 2013 May 22. PMID: 23698361. 17: Zimmermann G, Schultz-Fademrecht C, Küchler P, Murarka S, Ismail S, Triola G, Nussbaumer P, Wittinghofer A, Waldmann H. Structure guided design and kinetic analysis of highly potent benzimidazole inhibitors targeting the PDEδ prenyl binding site. J Med Chem. 2014 Jun 26;57(12):5435-48. doi: 10.1021/jm500632s. Epub 2014 Jun 11. PMID: 24884780.