Delanzomib (CEP-18770)
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MedKoo CAT#: 200713

CAS#: 847499-27-8

Description: 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

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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 Quantity
5.0mg USD 90.0 Same day
10.0mg USD 150.0 Same day
25.0mg USD 450.0 Same day
50.0mg USD 750.0 Same day
100.0mg USD 1150.0 Same day
200.0mg USD 1850.0 Same day
500.0mg USD 2650.0 Same day
1.0g USD 3450.0 2 Weeks
2.0g USD 5850.0 2 Weeks
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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

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 71.0 171.8
DMF 30.0 72.59
Ethanol 56.5 136.71

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.

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. 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: 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.
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.

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7. Rickles, Richard; Lee, Margaret S. Use of adenosine A2A receptor agonists and phosphodiesterase (PDE) inhibitors for the treatment of B-cell proliferative disorders, and combinations with other agents. PCT Int. Appl. (2009), 70 pp. CODEN: PIXXD2 WO 2009011893 A2 20090122 CAN 150:160095 AN 2009:86451

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9. Hoveyda, Hamid; Fraser, Graeme L.; Benakli, Kamel; Beauchemin, Sophie; Brassard, Martin; Drutz, David; Marsault, Eric; Ouellet, Luc; Peterson, Mark L.; Wang, Zhigang. Preparation and methods of using macrocyclic modulators of the ghrelin receptor. U.S. Pat. Appl. Publ. (2008), 178pp. CODEN: USXXCO US 2008194672 A1 20080814 CAN 149:288945 AN 2008:975261

10. Piva, Roberto; Ruggeri, Bruce; Williams, Michael; Costa, Giulia; Tamagno, Ilaria; Ferrero, Dario; Giai, Valentina; Coscia, Marta; Peola, Silvia; Massaia, Massimo; Pezzoni, Gabriella; Allievi, Cecilia; Pescalli, Nicoletta; Cassin, Mara; di Giovine, Stefano; Nicoli, Paola; de Feudis, Paola; Strepponi, Ivan; Roato, Ilaria; Ferracini, Riccardo; Bussolati, Benedetta; Camussi, Giovanni; Jones-Bolin, Susan; Hunter, Kathryn; Zhao, Hugh; Neri, Antonino; Palumbo, Antonio; Berkers, Celia; Ovaa, Huib; Bernareggi, Alberto; Inghirami, Giorgio. CEP-18770: a novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood (2008), 111(5), 2765-2775. CODEN: BLOOAW ISSN:0006-4971. CAN 149:486154 AN 2008:292777



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