WARNING: This product is for research use only, not for human or veterinary use.
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.
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
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/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 71.0 | 171.8 | |
| DMF | 30.0 | 72.59 | |
| Ethanol | 56.5 | 136.71 |
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: | 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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