Foscenvivint

Foscenvivint
Clinical data
Other names	PRI 724; OP 724
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name [4-[[(6S,9S,9aS)-1-(Benzylcarbamoyl)-2,9-dimethyl-4,7-dioxo-8-(quinolin-8-ylmethyl)-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazin-6-yl]methyl]phenyl] dihydrogen phosphate;
CAS Number	1422253-38-0;
PubChem CID	71509318;
DrugBank	DB15034;
UNII	43Y934BBZ6;
Chemical and physical data
Formula	C33H35N6O7P
Molar mass	658.652 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@H]1[C@H]2N([C@H](C(=O)N1CC3=CC=CC4=C3N=CC=C4)CC5=CC=C(C=C5)OP(=O)(O)O)C(=O)CN(N2C(=O)NCC6=CC=CC=C6)C;
	InChI InChI=1S/C33H35N6O7P/c1-22-31-38(29(40)21-36(2)39(31)33(42)35-19-24-8-4-3-5-9-24)28(18-23-13-15-27(16-14-23)46-47(43,44)45)32(41)37(22)20-26-11-6-10-25-12-7-17-34-30(25)26/h3-17,22,28,31H,18-21H2,1-2H3,(H,35,42)(H2,43,44,45)/t22-,28-,31-/m0/s1; Key:VHOZWHQPEJGPCC-AZXNYEMZSA-N;

Foscenvivint (PRI 724 or OP 724)^[1] is a CREB-binding protein/β-catenin inhibitor that is developed for the treatment of liver diseases^[2] such as primary biliary cholangitis,^[3] hepatocellular carcinoma,^[4]^[5] and hepatitis C and B virus-induced liver cirrhosis.^[6]^[7]

References

^ "Foscenvivint - PRISM Pharma Co - AdisInsight". adisinsight.springer.com. Retrieved 23 November 2023.
^ Ouchi, Hirofumi; Mizutani, Yuki; Yoshimura, Kaori; Sato, Yasunori; Kimura, Kiminori; Haruyama, Yushi; Harada, Kenichi (June 2023). "Anti-inflammatory and antifibrotic effects of CBP/β-catenin inhibitor for hepatocytes: small molecular inhibitor, OP-724 possibly improves liver function". Medical Molecular Morphology. 56 (2): 94–105. doi:10.1007/s00795-022-00343-8. PMID 36645521. S2CID 255847780.
^ Kimura, Masamichi; Ogawa, Eiichi; Harada, Kenichi; Imamura, Jun; Saio, Masanao; Ikura, Yoshihiro; Yatsuhashi, Hiroshi; Murata, Kazumoto; Miura, Kouichi; Ieiri, Ichiro; Tanaka, Atsushi; Kimura, Kiminori (1 November 2022). "Feasibility, safety and tolerability of the CREB-binding protein/β-catenin inhibitor OP-724 in patients with advanced primary biliary cholangitis: an investigator-initiated, open-label, non-randomised, two-centre, phase 1 study". BMJ Open Gastroenterology. 9 (1): e001001. doi:10.1136/bmjgast-2022-001001. ISSN 2054-4774. PMC 9710334. PMID 36442892.
^ El-Khoueiry, Anthony B.; Ning, Yan; Yang, Dongyun; Cole, Sarah; Kahn, Michael; Zoghbi, Marwan; Berg, Jennifer; Fujimori, Masamoto; Inada, Tetsuhi; Kouji, Hiroyuki; Lenz, Heinz-Josef (20 May 2013). "A phase I first-in-human study of PRI-724 in patients (pts) with advanced solid tumors". Journal of Clinical Oncology. 31 (15_suppl): 2501. doi:10.1200/jco.2013.31.15_suppl.2501.
^ Gabata, Ryosuke; Harada, Kenichi; Mizutani, Yuki; Ouchi, Hirofumi; Yoshimura, Kaori; Sato, Yasunori; Kitao, Azusa; Kimura, Kiminori; Kouji, Hiroyuki; Miyashita, Tomoharu; Tajima, Hidehiro; Ohta, Tetsuo (September 2020). "Anti-tumor Activity of the Small Molecule Inhibitor PRI-724 Against β-Catenin-activated Hepatocellular Carcinoma". Anticancer Research. 40 (9): 5211–5219. doi:10.21873/anticanres.14524. PMID 32878809.
^ Kimura, Kiminori; Kanto, Tatsuya; Shimoda, Shinji; Harada, Kenichi; Kimura, Masamichi; Nishikawa, Koji; Imamura, Jun; Ogawa, Eiichi; Saio, Masanao; Ikura, Yoshihiro; Okusaka, Takuji; Inoue, Kazuaki; Ishikawa, Tetsuya; Ieiri, Ichiro; Kishimoto, Junji; Todaka, Koji; Kamisawa, Terumi (June 2022). "Safety, tolerability, and anti-fibrotic efficacy of the CBP/β-catenin inhibitor PRI-724 in patients with hepatitis C and B virus-induced liver cirrhosis: An investigator-initiated, open-label, non-randomised, multicentre, phase 1/2a study". eBioMedicine. 80: 104069. doi:10.1016/j.ebiom.2022.104069. PMC 9126795. PMID 35605429.
^ Kimura, Kiminori; Ikoma, Akemi; Shibakawa, Maki; Shimoda, Shinji; Harada, Kenichi; Saio, Masanao; Imamura, Jun; Osawa, Yosuke; Kimura, Masamichi; Nishikawa, Koji; Okusaka, Takuji; Morita, Satoshi; Inoue, Kazuaki; Kanto, Tatsuya; Todaka, Koji; Nakanishi, Yoichi; Kohara, Michinori; Mizokami, Masashi (September 2017). "Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial". eBioMedicine. 23: 79–87. doi:10.1016/j.ebiom.2017.08.016. PMC 5605374. PMID 28844410.

[1] "Foscenvivint - PRISM Pharma Co - AdisInsight". adisinsight.springer.com. Retrieved 23 November 2023.

[2] Ouchi, Hirofumi; Mizutani, Yuki; Yoshimura, Kaori; Sato, Yasunori; Kimura, Kiminori; Haruyama, Yushi; Harada, Kenichi (June 2023). "Anti-inflammatory and antifibrotic effects of CBP/β-catenin inhibitor for hepatocytes: small molecular inhibitor, OP-724 possibly improves liver function". Medical Molecular Morphology. 56 (2): 94–105. doi:10.1007/s00795-022-00343-8. PMID 36645521. S2CID 255847780.

[3] Kimura, Masamichi; Ogawa, Eiichi; Harada, Kenichi; Imamura, Jun; Saio, Masanao; Ikura, Yoshihiro; Yatsuhashi, Hiroshi; Murata, Kazumoto; Miura, Kouichi; Ieiri, Ichiro; Tanaka, Atsushi; Kimura, Kiminori (1 November 2022). "Feasibility, safety and tolerability of the CREB-binding protein/β-catenin inhibitor OP-724 in patients with advanced primary biliary cholangitis: an investigator-initiated, open-label, non-randomised, two-centre, phase 1 study". BMJ Open Gastroenterology. 9 (1): e001001. doi:10.1136/bmjgast-2022-001001. ISSN 2054-4774. PMC 9710334. PMID 36442892.

[4] El-Khoueiry, Anthony B.; Ning, Yan; Yang, Dongyun; Cole, Sarah; Kahn, Michael; Zoghbi, Marwan; Berg, Jennifer; Fujimori, Masamoto; Inada, Tetsuhi; Kouji, Hiroyuki; Lenz, Heinz-Josef (20 May 2013). "A phase I first-in-human study of PRI-724 in patients (pts) with advanced solid tumors". Journal of Clinical Oncology. 31 (15_suppl): 2501. doi:10.1200/jco.2013.31.15_suppl.2501.

[5] Gabata, Ryosuke; Harada, Kenichi; Mizutani, Yuki; Ouchi, Hirofumi; Yoshimura, Kaori; Sato, Yasunori; Kitao, Azusa; Kimura, Kiminori; Kouji, Hiroyuki; Miyashita, Tomoharu; Tajima, Hidehiro; Ohta, Tetsuo (September 2020). "Anti-tumor Activity of the Small Molecule Inhibitor PRI-724 Against β-Catenin-activated Hepatocellular Carcinoma". Anticancer Research. 40 (9): 5211–5219. doi:10.21873/anticanres.14524. PMID 32878809.

[6] Kimura, Kiminori; Kanto, Tatsuya; Shimoda, Shinji; Harada, Kenichi; Kimura, Masamichi; Nishikawa, Koji; Imamura, Jun; Ogawa, Eiichi; Saio, Masanao; Ikura, Yoshihiro; Okusaka, Takuji; Inoue, Kazuaki; Ishikawa, Tetsuya; Ieiri, Ichiro; Kishimoto, Junji; Todaka, Koji; Kamisawa, Terumi (June 2022). "Safety, tolerability, and anti-fibrotic efficacy of the CBP/β-catenin inhibitor PRI-724 in patients with hepatitis C and B virus-induced liver cirrhosis: An investigator-initiated, open-label, non-randomised, multicentre, phase 1/2a study". eBioMedicine. 80: 104069. doi:10.1016/j.ebiom.2022.104069. PMC 9126795. PMID 35605429.

[7] Kimura, Kiminori; Ikoma, Akemi; Shibakawa, Maki; Shimoda, Shinji; Harada, Kenichi; Saio, Masanao; Imamura, Jun; Osawa, Yosuke; Kimura, Masamichi; Nishikawa, Koji; Okusaka, Takuji; Morita, Satoshi; Inoue, Kazuaki; Kanto, Tatsuya; Todaka, Koji; Nakanishi, Yoichi; Kohara, Michinori; Mizokami, Masashi (September 2017). "Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial". eBioMedicine. 23: 79–87. doi:10.1016/j.ebiom.2017.08.016. PMC 5605374. PMID 28844410.

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