Delanzomib | CEP-18770 | CAS#847499-27-8

MedKoo Cat#: 200713 | Name: Delanzomib (CEP-18770)

Description:

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

Delanzomib, also known as CEP-18770, is An orally bioavailable synthetic P2 threonine boronic acid inhibitor of the chymotrypsin-like activity of the proteasome, with potential antineoplastic activity. Proteasome inhibitor CEP 18770 represses the proteasomal degradation of a variety of proteins, including inhibitory kappaBalpha (IkappaBalpha), resulting in the cytoplasmic sequestration of the transcription factor NF-kappaB; inhibition of NF-kappaB nuclear translocation and transcriptional up-regulation of a variety of cell growth-promoting factors; and apoptotic cell death in susceptible tumor cell populations.

Chemical Structure

Delanzomib (CEP-18770)

CAS#847499-27-8

Theoretical Analysis

MedKoo Cat#: 200713

Name: Delanzomib (CEP-18770)

CAS#: 847499-27-8

Chemical Formula: C21H28BN3O5

Exact Mass: 413.2122

Molecular Weight: 413.27

Elemental Analysis: C, 61.03; H, 6.83; B, 2.62; N, 10.17; O, 19.36

Price and Availability

Size	Price	Availability
5mg	USD 120.00	Ready to ship
10mg	USD 200.00	Ready to ship
25mg	USD 400.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,350.00	Ready to ship
200mg	USD 2,350.00	Ready to ship

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Related CAS #

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Synonym

CEP18770; CEP 18770; CEP-18770; Delanzomib

IUPAC/Chemical Name

[(1R)-1-[[(2S,3R)-3-Hydroxy-2-[[(6-phenylpyridin-2-yl)carbonyl]amino]-1-oxobutyl]amino]-3-methylbutyl]boronic acid.

InChi Key

SJFBTAPEPRWNKH-CCKFTAQKSA-N

InChi Code

InChI=1S/C21H28BN3O5/c1-13(2)12-18(22(29)30)24-21(28)19(14(3)26)25-20(27)17-11-7-10-16(23-17)15-8-5-4-6-9-15/h4-11,13-14,18-19,26,29-30H,12H2,1-3H3,(H,24,28)(H,25,27)/t14-,18+,19+/m1/s1

SMILES Code

CC(C)C[C@@H](B(O)O)NC([C@@H](NC(C1=NC(C2=CC=CC=C2)=CC=C1)=O)[C@H](O)C)=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, not in water

Shelf Life

>5 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#TZC60504

QC Data

View QC data: current batch, Lot#TZC60504

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Delanzomib (CEP-18770) is a chymotrypsin-like activity of the proteasome inhibitor with an IC50 of 3.8 nM.

In vitro activity:

As shown in Figure 4C, delanzomib could up-regulate ERS-associated proteins in a concentration-dependent manner in both sorafenib sensitive and resistant HCC cells. After treatment with delanzomib on SK-hep-1 and SK-sora-5 cells for 48 h, the protein levels of p-PERK and p-eIF2α were significantly increased, whereas total PERK and eIF2α remained unchanged. Moreover, the protein levels of ATF4 and CHOP were also increased (The Original image of WB scan is shown in the Supplementary Figure 5). To further verify the role of ERS in delanzomib-induced apoptosis, salubrinal as a selective inhibitor of eIF2α dephosphorylation, was adopted to co-treated HCC cells with delanzomib. Interestingly, salubrinal significantly reduced delanzomib-induced apoptosis in both HCC cells (Figure 4D). The ratio of apoptotic cells decreased from 25.7% to 12.3% for SK-hep-1 (P<0.01) and from 22.8% to 11.5% for SK-sora-5 (P<0.01), respectively. All these data demonstrated that delanzomib could induce the activation of ERS, and ERS could trigger delanzomib-induced apoptosis through the PERK/eIF2α/ATF4/CHOP pathway in HCC cells despite they were sensitive or resistant to sorafenib. Reference: Am J Transl Res. 2020; 12(6): 2875–2889. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344101/

In vivo activity:

Treatment of SLE-prone, proteinuria-positive NZM mice with delanzomib extended survival significantly over vehicle (55% and 46% respectively; p < 0.001) and significantly extended survival over that of both CTX and both bortezomib treatment groups (p < 0.01) (Fig. S3D) (p < 0.001). Both 20S proteasome activity and IκBα accumulation were used as pharmacodynamic indicators of delanzomib-mediated proteasome inhibition in the spleen and kidneys of treated NZM mice. Once and twice weekly administration of delanzomib inhibited spleen 20S proteasome activity as compared to vehicle treatment (p < 0.05) (40% inhibition relative to vehicle) (Fig. S4A). Twice, but not once, weekly administration of delanzomib increased the accumulation of kidney IĸBα levels above that of the vehicle-treatment (40% increase, p < 0.05) (Fig. S4B). Reference: Int Immunopharmacol. 2012 Jan;12(1):257-70. https://pubmed.ncbi.nlm.nih.gov/22178195/

	Solvent	mg/mL	mM
Solubility
	DMSO	71.0	171.80
	DMF	30.0	72.59
	Ethanol	56.5	136.71

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 413.27 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. Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. Proteasome or immunoproteasome inhibitors cause apoptosis in human renal tubular epithelial cells under normoxic and hypoxic conditions. Int Urol Nephrol. 2016 Jun;48(6):907-15. doi: 10.1007/s11255-016-1247-6. Epub 2016 Feb 26. PMID: 26920131. 2. Li J, Zhuo JY, Zhou W, Hong JW, Chen RG, Xie HY, Zhou L, Zheng SS, Jiang DH. Endoplasmic reticulum stress triggers delanzomib-induced apoptosis in HCC cells through the PERK/eIF2α/ATF4/CHOP pathway. Am J Transl Res. 2020 Jun 15;12(6):2875-2889. PMID: 32655816; PMCID: PMC7344101. 3. Seavey MM, Lu LD, Stump KL, Wallace NH, Ruggeri BA. Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE. Int Immunopharmacol. 2012 Jan;12(1):257-70. doi: 10.1016/j.intimp.2011.11.019. Epub 2011 Dec 13. PMID: 22178195.

In vitro protocol:

In vivo protocol:

1. Seavey MM, Lu LD, Stump KL, Wallace NH, Ruggeri BA. Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE. Int Immunopharmacol. 2012 Jan;12(1):257-70. doi: 10.1016/j.intimp.2011.11.019. Epub 2011 Dec 13. PMID: 22178195. 2. Li J, Zhuo JY, Zhou W, Hong JW, Chen RG, Xie HY, Zhou L, Zheng SS, Jiang DH. Endoplasmic reticulum stress triggers delanzomib-induced apoptosis in HCC cells through the PERK/eIF2α/ATF4/CHOP pathway. Am J Transl Res. 2020 Jun 15;12(6):2875-2889. PMID: 32655816; PMCID: PMC7344101.

1: Sanchez E, Li M, Li J, Wang C, Chen H, Jones-Bolin S, Hunter K, Ruggeri B, Berenson JR. CEP-18770 (delanzomib) in combination with dexamethasone and lenalidomide inhibits the growth of multiple myeloma. Leuk Res. 2012 Nov;36(11):1422-7. doi: 10.1016/j.leukres.2012.07.018. Epub 2012 Aug 17. PMID: 22906694. 2: Narayanan S, Cai CY, Assaraf YG, Guo HQ, Cui Q, Wei L, Huang JJ, Ashby CR Jr, Chen ZS. Targeting the ubiquitin-proteasome pathway to overcome anti-cancer drug resistance. Drug Resist Updat. 2020 Jan;48:100663. doi: 10.1016/j.drup.2019.100663. Epub 2019 Nov 11. PMID: 31785545. 3: Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D, Giai V, Coscia M, Peola S, Massaia M, Pezzoni G, Allievi C, Pescalli N, Cassin M, di Giovine S, Nicoli P, de Feudis P, Strepponi I, Roato I, Ferracini R, Bussolati B, Camussi G, Jones-Bolin S, Hunter K, Zhao H, Neri A, Palumbo A, Berkers C, Ovaa H, Bernareggi A, Inghirami G. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood. 2008 Mar 1;111(5):2765-75. doi: 10.1182/blood-2007-07-100651. Epub 2007 Dec 5. PMID: 18057228. 4: Seavey MM, Lu LD, Stump KL, Wallace NH, Ruggeri BA. Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE. Int Immunopharmacol. 2012 Jan;12(1):257-70. doi: 10.1016/j.intimp.2011.11.019. Epub 2011 Dec 13. PMID: 22178195. 5: Vogl DT, Martin TG, Vij R, Hari P, Mikhael JR, Siegel D, Wu KL, Delforge M, Gasparetto C. Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma. Leuk Lymphoma. 2017 Aug;58(8):1872-1879. doi: 10.1080/10428194.2016.1263842. Epub 2017 Jan 31. PMID: 28140719. 6: Sanchez E, Li M, Steinberg JA, Wang C, Shen J, Bonavida B, Li ZW, Chen H, Berenson JR. The proteasome inhibitor CEP-18770 enhances the anti-myeloma activity of bortezomib and melphalan. Br J Haematol. 2010 Feb;148(4):569-81. doi: 10.1111/j.1365-2141.2009.08008.x. Epub 2009 Dec 1. PMID: 19958357. 7: Gallerani E, Zucchetti M, Brunelli D, Marangon E, Noberasco C, Hess D, Delmonte A, Martinelli G, Böhm S, Driessen C, De Braud F, Marsoni S, Cereda R, Sala F, D'Incalci M, Sessa C. A first in human phase I study of the proteasome inhibitor CEP-18770 in patients with advanced solid tumours and multiple myeloma. Eur J Cancer. 2013 Jan;49(2):290-6. doi: 10.1016/j.ejca.2012.09.009. Epub 2012 Oct 8. PMID: 23058787. 8: Kegyes D, Gulei D, Drula R, Cenariu D, Tigu B, Dima D, Tanase A, Badelita S, Buzoianu AD, Ciurea S, Ghiaur G, Terpos E, Ciechanover A, Einsele H, Tomuleasa C. Proteasome inhibition in combination with immunotherapies: State-of-the-Art in multiple myeloma. Blood Rev. 2023 Sep;61:101100. doi: 10.1016/j.blre.2023.101100. Epub 2023 May 27. PMID: 37291017. 9: Teicher BA, Tomaszewski JE. Proteasome inhibitors. Biochem Pharmacol. 2015 Jul 1;96(1):1-9. doi: 10.1016/j.bcp.2015.04.008. Epub 2015 Apr 29. PMID: 25935605. 10: Wang M, Liang L, Lu J, Yu Y, Zhao Y, Shi Z, Li H, Xu X, Yan Y, Niu Y, Liu Z, Shen L, Zhang H. Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin-induced apoptosis. Thorac Cancer. 2019 Apr;10(4):918-929. doi: 10.1111/1759-7714.13030. Epub 2019 Mar 18. PMID: 30883017; PMCID: PMC6449274. 11: Sala F, Marangon E, Bagnati R, Livi V, Cereda R, D'Incalci M, Zucchetti M. Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the determination of the novel proteasome inhibitor CEP-18770 in human plasma and its application in a clinical pharmacokinetic study. J Mass Spectrom. 2010 Nov;45(11):1299-305. doi: 10.1002/jms.1842. Epub 2010 Sep 25. PMID: 20872901. 12: Isono M, Sato A, Asano T, Okubo K, Asano T. Delanzomib Interacts with Ritonavir Synergistically to Cause Endoplasmic Reticulum Stress in Renal Cancer Cells. Anticancer Res. 2018 Jun;38(6):3493-3500. doi: 10.21873/anticanres.12620. PMID: 29848702. 13: Romaniuk W, Ołdziej AE, Zińczuk J, Kłoczko J. Inhibitory proteasomów w terapii onkologicznej [Proteasome inhibitors in cancer therapy]. Postepy Hig Med Dosw (Online). 2015 Dec 31;69:1443-50. Polish. PMID: 27259216. 14: Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. A comparative analysis between proteasome and immunoproteasome inhibition in cellular and humoral alloimmunity. Int Immunopharmacol. 2017 Sep;50:48-54. doi: 10.1016/j.intimp.2017.06.009. Epub 2017 Jun 16. PMID: 28628770. 15: Li J, Zhuo JY, Zhou W, Hong JW, Chen RG, Xie HY, Zhou L, Zheng SS, Jiang DH. Endoplasmic reticulum stress triggers delanzomib-induced apoptosis in HCC cells through the PERK/eIF2α/ATF4/CHOP pathway. Am J Transl Res. 2020 Jun 15;12(6):2875-2889. PMID: 32655816; PMCID: PMC7344101. 16: Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. Proteasome or immunoproteasome inhibitors cause apoptosis in human renal tubular epithelial cells under normoxic and hypoxic conditions. Int Urol Nephrol. 2016 Jun;48(6):907-15. doi: 10.1007/s11255-016-1247-6. Epub 2016 Feb 26. PMID: 26920131. 17: Wang L, Liu L, Hong X, Liu D, Cheng Z. Delanzomib, a Novel Proteasome Inhibitor, Combined With Adalimumab Drastically Ameliorates Collagen-Induced Arthritis in Rats by Improving and Prolonging the Anti-TNF-α Effect of Adalimumab. Front Pharmacol. 2021 Nov 22;12:782385. doi: 10.3389/fphar.2021.782385. PMID: 34880764; PMCID: PMC8645831. 18: Guo KY, Han L, Li X, Yang AV, Lu J, Guan S, Li H, Yu Y, Zhao Y, Yang J, Zhang H. Novel proteasome inhibitor delanzomib sensitizes cervical cancer cells to doxorubicin-induced apoptosis via stabilizing tumor suppressor proteins in the p53 pathway. Oncotarget. 2017 Dec 12;8(69):114123-114135. doi: 10.18632/oncotarget.23166. PMID: 29371974; PMCID: PMC5768391. 19: Zangari M, Suva LJ. The effects of proteasome inhibitors on bone remodeling in multiple myeloma. Bone. 2016 May;86:131-8. doi: 10.1016/j.bone.2016.02.019. Epub 2016 Mar 3. PMID: 26947893; PMCID: PMC5516941. 20: Berkers CR, Leestemaker Y, Schuurman KG, Ruggeri B, Jones-Bolin S, Williams M, Ovaa H. Probing the specificity and activity profiles of the proteasome inhibitors bortezomib and delanzomib. Mol Pharm. 2012 May 7;9(5):1126-35. doi: 10.1021/mp2004143. Epub 2012 Apr 16. PMID: 22432738.