Diprovocim

• CAT Number: I026281
• CAS Number: 2170867-89-5
• Molecular Formula: C56H56N6O6
• Molecular Weight: 909.1
• Purity: 98%
• Synonyms: Diprovocim; Diprovocim-1
• Target: Apoptosis
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Storage: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
• IUPAC Name: (3S,3'S,4S,4'S)-1,1'-terephthaloylbis(N3,N4-bis((1S,2R)-2-phenylcyclopropyl)pyrrolidine-3,4-dicarboxamide)
• InChI: InChI=1S/C56H56N6O6/c63-51(57-47-25-39(47)33-13-5-1-6-14-33)43-29-61(30-44(43)52(64)58-48-26-40(48)34-15-7-2-8-16-34)55(67)37-21-23-38(24-22-37)56(68)62-31-45(53(65)59-49-27-41(49)35-17-9-3-10-18-35)46(32-62)54(66)60-50-28-42(50)36-19-11-4-12-20-36/h1-24,39-50H,25-32H2,(H,57,63)(H,58,64)(H,59,65)(H,60,66)/t39-,40-,41-,42-,43-,44-,45-,46-,47+,48+,49+,50+/m1/s1
• InChIKey: ABZBNXFGYUSVCJ-UYMKNZQYSA-N
• SMILES: O=C(N1C[C@@H](C(N[C@@H]2[C@@H](C3=CC=CC=C3)C2)=O)[C@H](C(N[C@@H]4[C@@H](C5=CC=CC=C5)C4)=O)C1)C6=CC=C(C(N7C[C@@H](C(N[C@@H]8[C@@H](C9=CC=CC=C9)C8)=O)[C@H](C(N[C@@H]%10[C@@H](C%11=CC=CC=C%11)C%10)=O)C7)=O)C=C6

Diprovocim is a potent Toll-like receptor TLR1/TLR2 agonist that induces dose-dependent TNF production with EC50 of 110 pM. Diprovocim has shown significant adjuvant activity in anticancer vaccination against murine melanoma. Diprovocim exhibited an EC50 of 110 pM in human THP-1 cells and 1.3 nM in primary mouse peritoneal macrophages. In mice, Diprovocim-adjuvanted ovalbumin immunization promoted antigen-specific humoral and CTL responses and synergized with anti-PD-L1 treatment to inhibit tumor growth, generating long-term antitumor memory, curing or prolonging survival of mice engrafted with the murine melanoma B16-OVA. Diprovocim induced greater frequencies of tumor-infiltrating leukocytes than alum, of which CD8 T cells were necessary for the antitumor effect of immunization plus anti-PD-L1 treatment.

Reference

1: Su L, Wang Y, Wang J, Mifune Y, Morin MD, Jones BT, Moresco EM, Boger DL,
Beutler B, Zhang H. Structural basis of TLR2/TLR1 activation by the synthetic
agonist Diprovocim. J Med Chem. 2019 Mar 4. doi: 10.1021/acs.jmedchem.8b01583.
[Epub ahead of print] PubMed PMID: 30829478.
2: Morin MD, Wang Y, Jones BT, Mifune Y, Su L, Shi H, Moresco EMY, Zhang H,
Beutler B, Boger DL. Diprovocims: A New and Exceptionally Potent Class of
Toll-like Receptor Agonists. J Am Chem Soc. 2018 Oct 31;140(43):14440-14454. doi:
10.1021/jacs.8b09223. Epub 2018 Oct 16. PubMed PMID: 30272974; PubMed Central
PMCID: PMC6209530.
3: Wang Y, Su L, Morin MD, Jones BT, Mifune Y, Shi H, Wang KW, Zhan X, Liu A,
Wang J, Li X, Tang M, Ludwig S, Hildebrand S, Zhou K, Siegwart DJ, Moresco EMY,
Zhang H, Boger DL, Beutler B. Adjuvant effect of the novel TLR1/TLR2 agonist
Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice. Proc Natl
Acad Sci U S A. 2018 Sep 11;115(37):E8698-E8706. doi: 10.1073/pnas.1809232115.
Epub 2018 Aug 27. PubMed PMID: 30150374; PubMed Central PMCID: PMC6140543.