Cenicriviroc - Misplaced Pages

Cenicriviroc
Names

Preferred IUPAC name (5E)-8--1-(2-methylpropyl)-N-{4-phenyl}-1,2,3,4-tetrahydro-1-benzazocine-5-carboxamide
Other names TAK-652; TBR-652
Identifiers
CAS Number	497223-25-3 497223-28-6 (mesylate)
3D model (JSmol)	Interactive image
ChEBI	CHEBI:149636
ChEMBL	ChEMBL2110727
ChemSpider	9460783
IUPHAR/BPS	801
KEGG	D09878
PubChem CID	11285792 11285792
UNII	15C116UA4Y R96TV84T21 (mesylate)
CompTox Dashboard (EPA)	DTXSID80964373
InChI InChI=1S/C41H52N4O4S/c1-5-7-22-48-23-24-49-38-15-10-32(11-16-38)33-12-19-40-35(25-33)26-34(9-8-21-44(40)28-31(3)4)41(46)43-36-13-17-39(18-14-36)50(47)29-37-27-42-30-45(37)20-6-2/h10-19,25-27,30-31H,5-9,20-24,28-29H2,1-4H3,(H,43,46)/b34-26+/t50-/m0/s1Key: PNDKCRDVVKJPKG-WHERJAGFSA-N InChI=1/C41H52N4O4S/c1-5-7-22-48-23-24-49-38-15-10-32(11-16-38)33-12-19-40-35(25-33)26-34(9-8-21-44(40)28-31(3)4)41(46)43-36-13-17-39(18-14-36)50(47)29-37-27-42-30-45(37)20-6-2/h10-19,25-27,30-31H,5-9,20-24,28-29H2,1-4H3,(H,43,46)/b34-26+/t50-/m0/s1Key: PNDKCRDVVKJPKG-WHERJAGFBH
SMILES O=S(c1ccc(cc1)NC(=O)\C4=C\c3c(ccc(c2ccc(OCCOCCCC)cc2)c3)N(CCC4)CC(C)C)Cc5cncn5CCC
Properties
Chemical formula	C₄₁H₅₂N₄O₄S
Molar mass	696.95 g·mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). N verify (what is ?) Infobox references

Chemical compound

Cenicriviroc (INN, code names TAK-652, TBR-652, commonly abbreviated as CVC) is an experimental drug candidate for the treatment of HIV infection and in combination with Tropifexor for non-alcoholic steatohepatitis. It is being developed by Takeda and Tobira Therapeutics.

Cenicriviroc is an inhibitor of CCR2 and CCR5 receptors, allowing it to function as an entry inhibitor which prevents the virus from entering into a human cell. Inhibition of CCR2 may have an anti-inflammatory effect.

A double-blind, randomized, placebo-controlled clinical study to assess the antiviral activity, safety, and tolerability of cenicriviroc was conducted in 2010. HIV-infected patients taking cenicriviroc had significant reductions in viral load, with the effect persisting up to two weeks after discontinuation of treatment. Additional Phase II clinical trials are underway.

Cenicriviroc is also in two separate clinical trials for COVID-19: the ACTIV-I trial run by the National Center for Advancing Translational Sciences, where it is compared with a number of other immunomodulatory agents, and the Charité Trial of Cenicriviroc at the Charité Hospital in Berlin. As of 2 July 2021, both trials are recruiting participants, and are expected to complete in September 2021.

Phase IIb data presented at the 20th Conference on Retroviruses and Opportunistic Infections (CROI) in March 2013 showed similar viral suppression rates of 76% for patients taking 100 mg cenicriviroc, 73% with 200 mg cenicriviroc, and 71% with efavirenz. Non-response rates were higher with cenicriviroc, however, largely due to greater drop-out of patients. A new tablet formulation with lower pill burden may improve adherence. Looking at immune and inflammatory biomarkers, levels of MCP-1 increased and soluble CD14 decreased in the cenicriviroc arms.

References

"International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 65" (PDF). World Health Organization. 2011. pp. 53–4. Retrieved 25 November 2016.
Klibanov, OM; Williams, SH; Iler, CA (August 2010). "Cenicriviroc, an Orally Active CCR5 Antagonist for the Potential Treatment of HIV Infection". Current Opinion in Investigational Drugs. 11 (8): 940–50. PMID 20721836.
"A Randomized, Double-blind, Multicenter Study to Assess the Safety, Tolerability, and Efficacy of a Combination Treatment of Tropifexor (LJN452) and Cenicriviroc (CVC) in Adult Patients with Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis". 21 January 2022.
Baba, M; Takashima, K; Miyake, H; Kanzaki, N; Teshima, K; Wang, X; Shiraishi, M; Iizawa, Y (26 October 2005). "TAK-652 Inhibits CCR5-Mediated Human Immunodeficiency Virus Type 1 Infection In Vitro and Has Favorable Pharmacokinetics in Humans". Antimicrobial Agents and Chemotherapy. 49 (11): 4584–91. doi:10.1128/AAC.49.11.4584-4591.2005. PMC 1280155. PMID 16251299.
Reviriego, C (July 2011). "Chemokine CCR2/CCR5 Receptor Antagonist Anti-HIV Agent". Drugs of the Future. 36 (7): 511–7. doi:10.1358/dof.2011.036.07.1622066.
"Tobira Therapeutics Initiates Phase 2b Trial of Cenicriviroc". The Body. July 5, 2011.
Benjamin, Daniel (2021-06-29). "Randomized Master Protocol for Immune Modulators for Treating COVID-19". Daniel Benjamin, National Center for Advancing Translational Science (NCATS), Biomedical Advanced Research and Development Authority.
Tacke, Frank (2020-08-25). "Charité Trial of Cenicriviroc (CVC) Treatment for COVID-19 Patients". Charite University, Berlin, Germany, Allergan.
CROI 2013: CCR5/CCR2 Inhibitor Cenicriviroc Has Both Anti-HIV and Anti-inflammatory Effects. Highleyman, Liz. HIVandHepatitis.com. 7 March 2013.

Antiviral drugs: antiretroviral drugs used against HIV (primarily J05)

Capsid inhibitors

Lenacapavir (LEN)

Entry/fusion inhibitors
(Discovery and development)

Integrase inhibitors
(Integrase strand transfer inhibitors (INSTI))

Maturation inhibitors

Protease Inhibitors (PI)
(Discovery and development)

1 generation	Amprenavir (APV) Fosamprenavir (FPV) Indinavir (IDV) Lopinavir (LPV) Nelfinavir (NFV) Ritonavir (RTV) Saquinavir (SQV)
2 generation	Atazanavir (ATV)° Darunavir (DRV)° Tipranavir (TPV) TMC-310911

Reverse-transcriptase
inhibitors (RTIs)

Nucleoside and
nucleotide (NRTI)

Non-nucleoside (NNRTI)
(Discovery and development)

1 generation	Efavirenz (EFV) Nevirapine (NVP) Delavirdine (DLV)
2 generation	diarylpyrimidines Dapivirine (DPV) Etravirine (ETR) Rilpivirine (RPV) Doravirine (DOR) Elsulfavirine (ESV)

Combined formulations

Pharmacokinetic boosters

Experimental agents

Uncoating inhibitors	TRIM5alpha (gene)
Transcription inhibitors	Tat antagonists
Translation inhibitors	Trichosanthin
BNAbs	Elipovimab
Other	Abzyme BIT225 Calanolide A Ceragenin Cyanovirin-N Diarylpyrimidines Epigallocatechin gallate (EGCG) Foscarnet Fosdevirine Griffithsin Hydroxycarbamide KP-1461 Miltefosine Portmanteau inhibitors Scytovirin Seliciclib Synergistic enhancers Tre recombinase Zinc finger protein transcription factor
Failed agents	Aplaviroc Atevirdine Brecanavir Capravirine Dexelvucitabine Droxinavir Lasinavir Emivirine Lersivirine Lodenosine Loviride Mozenavir Palinavir Telinavir

WHO-EM
Withdrawn from market
Clinical trials:
- Phase III
- Never to phase III

°DHHS recommended initial regimen options. Formerly or rarely used agent.

Chemokine receptor modulators

CCR1	Agonists: CCL4 (MIP-1β) CCL5 (RANTES) CCL6 CCL9 (CCL10) CCL14 CCL15 CCL16 CCL23
CCR2	Agonists: CCL2 CCL8 CCL12 CCL16 NAMs: Cenicriviroc (TAK-652, TBR-652)
CCR3	Agonists: CCL5 (RANTES) CCL7 CCL11 CCL13 CCL15 CCL18 CCL24 CCL26 CCL28
CCR4	Agonists: CCL3 (MIP-1α) CCL5 (RANTES) CCL17 CCL22 Antibodies: Mogamulizumab (against CCR4)
CCR5	Agonists: CCL3 (MIP-1α) CCL4 (MIP-1β) CCL5 (RANTES) CCL8 CCL11 CCL13 CCL14 CCL16 NAMs: Aplaviroc Cenicriviroc (TAK-652, TBR-652) INCB009471 Maraviroc Vicriviroc Antibodies: PRO-140
CCR6	Agonists: CCL20
CCR7	Agonists: CCL19 CCL21
CCR8	Agonists: CCL1 CCL16
CCR9	Agonists: CCL25
CCR10	Agonists: CCL27 CCL28
CCR11	Agonists: CCL19 CCL21 CCL25
Ungrouped	Antibodies: Bertilimumab (against CCL11) Carlumab (against CCL2)

CXC

CXCR1 (IL-8Rα)	Agonists: CXCL6 Emoctakin Interleukin-8 (CXCL8, GCP-1) Antagonists: Navarixin NAMs: Ladarixin Reparixin (repertaxin)
CXCR2 (IL-8Rβ)	Agonists: CXCL1 (MGSA) CXCL2 CXCL3 CXCL5 CXCL6 CXCL7 Emoctakin Garnocestim Interleukin-8 (CXCL8, GCP-1) Antagonists: Danirixin Elubrixin Navarixin NAMs: Ladarixin Reparixin (repertaxin)
CXCR3	Agonists: CXCL4 (PF4) CXCL9 (MIG) CXCL10 (IP-10) CXCL11 (I-TAC) Iroplact Antibodies: Eldelumab (against CXCL10)
CXCR4	Agonists: MIF SDF-1 (CXCL12) Ubiquitin Antagonists: Mavorixafor Plerixafor (AMD3100) Antibodies: Ulocuplumab (against CXCR4)
CXCR5	Agonists: CXCL13
CXCR6	Agonists: CXCL16
CXCR7	Agonists: Conolidine CXCL11 (I-TAC) CCX771 LIH383 RTI-5152-12 SDF-1 (CXCL12) VUF15485 PAMs: Plerixafor (AMD3100)

C (XC)

XCR1	Agonists: Lymphotactin-α (XCL1) Lymphotactin-β (XCL2) Antibodies: Pateclizumab

CX3C

CX3CR1	Agonists: Fractalkine (CX3CL1)

Others

CCBP2	Agonists: CC (β) chemokines
CMKLR1	Agonists: Chemerin Resolvin E1

Categories:

See also

References