Cenicriviroc

{{Chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 451756573

| ImageFile = Cenicriviroc.svg

| ImageSize = 315px

| ImageAlt =

| PIN = (5E)-8-[4-(2-Butoxyethoxy)phenyl]-1-(2-methylpropyl)-N-{4-[(S)-(1-propyl-1H-imidazol-5-yl)methanesulfinyl]phenyl}-1,2,3,4-tetrahydro-1-benzazocine-5-carboxamide

| OtherNames = TAK-652; TBR-652

| Section1 = {{Chembox Identifiers

| IUPHAR_ligand = 801

| CASNo = 497223-25-3

| CASNo_Ref = {{cascite|correct|??}}

| CASNo1 = 497223-28-6

| CASNo1_Ref = {{cascite|correct|CAS}}

| CASNo1_Comment = (mesylate)

| PubChem = 11285792

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 15C116UA4Y

| UNII1_Ref = {{fdacite|correct|FDA}}

| UNII1 = R96TV84T21

| UNII1_Comment = (mesylate)

| ChEBI = 149636

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 2110727

| PubChem1 = 11285792

| KEGG = D09878

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 9460783

| SMILES = O=S(c1ccc(cc1)NC(=O)\C4=C\c3c(ccc(c2ccc(OCCOCCCC)cc2)c3)N(CCC4)CC(C)C)Cc5cncn5CCC

| 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/s1

| InChIKey = PNDKCRDVVKJPKG-WHERJAGFBH

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 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/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = PNDKCRDVVKJPKG-WHERJAGFSA-N}}

| Section2 = {{Chembox Properties

| C=41 | H=52 | N=4 | O=4 | S=1

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| Section3 = {{Chembox Hazards

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Cenicriviroc (INN,{{cite web | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 65 | url =https://www.who.int/medicines/publications/druginformation/innlists/RL65.pdf | publisher = World Health Organization | access-date = 25 November 2016 | pages = 53–4 | date = 2011}} code names TAK-652, TBR-652, commonly abbreviated as CVC) is an experimental drug candidate for the treatment of HIV infection{{cite journal | last1 = Klibanov | first1 = OM | last2 = Williams | first2 = SH | last3 = Iler | first3 = CA | title = Cenicriviroc, an Orally Active CCR5 Antagonist for the Potential Treatment of HIV Infection | journal = Current Opinion in Investigational Drugs | date = August 2010 | volume = 11 | issue = 8 | pages = 940–50 | pmid = 20721836}} and in combination with Tropifexor for non-alcoholic steatohepatitis.{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT03517540|title = 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|date = 21 January 2022}} It is being developed by Takeda and Tobira Therapeutics.{{cn|date=January 2023}}

Cenicriviroc is an inhibitor of CCR2 and CCR5 receptors,{{cite journal | last1 = Baba | first1 = M | last2 = Takashima | first2 = K | last3 = Miyake | first3 = H | last4 = Kanzaki | first4 = N | last5 = Teshima | first5 = K | last6 = Wang | first6 = X | last7 = Shiraishi | first7 = M | last8 = Iizawa | first8 = Y | title = TAK-652 Inhibits CCR5-Mediated Human Immunodeficiency Virus Type 1 Infection In Vitro and Has Favorable Pharmacokinetics in Humans | journal = Antimicrobial Agents and Chemotherapy | date = 26 October 2005 | volume = 49 | issue = 11 | pages = 4584–91 | doi = 10.1128/AAC.49.11.4584-4591.2005 | pmid = 16251299 | pmc = 1280155}} 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.{{cn|date=April 2021}}

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.{{cite journal | last1 = Reviriego | first1 = C | title = Chemokine CCR2/CCR5 Receptor Antagonist Anti-HIV Agent | journal = Drugs of the Future | date = July 2011 | volume = 36 | issue = 7 | pages = 511–7 | doi = 10.1358/dof.2011.036.07.1622066}} Additional Phase II clinical trials are underway.{{cite web | url = http://www.thebody.com/content/62837/tobira-therapeutics-initiates-phase-2b-trial-of-ce.html | title = Tobira Therapeutics Initiates Phase 2b Trial of Cenicriviroc | publisher = The Body | date = July 5, 2011}}{{When?|date=July 2021}}

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,{{Cite web|last=Benjamin|first=Daniel|date=2021-06-29|others=Daniel Benjamin, National Center for Advancing Translational Science (NCATS), Biomedical Advanced Research and Development Authority|title=Randomized Master Protocol for Immune Modulators for Treating COVID-19|url=https://clinicaltrials.gov/ct2/show/NCT04593940}} and the Charité Trial of Cenicriviroc at the Charité Hospital in Berlin.{{Cite web|last=Tacke|first=Frank|date=2020-08-25|others=Charite University, Berlin, Germany, Allergan|title=Charité Trial of Cenicriviroc (CVC) Treatment for COVID-19 Patients|url=https://clinicaltrials.gov/ct2/show/NCT04500418|journal=}} {{As of|2021|July|2}}, both trials are recruiting participants, and are expected to complete in September 2021.{{cn|date=September 2022}}

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.[http://www.hivandhepatitis.com/hiv-aids/hiv-aids-topics/hiv-treatment/4009-croi-2013-dual-ccr5ccr2-inhibitor-cenicriviroc-has-both-anti-hiv-and-anti-inflammatory-effects CROI 2013: CCR5/CCR2 Inhibitor Cenicriviroc Has Both Anti-HIV and Anti-inflammatory Effects]. Highleyman, Liz. HIVandHepatitis.com. 7 March 2013.