Cenicriviroc

Cenicriviroc
Names
	IUPAC name (S,E)-8-(4-(2-Butoxyethoxy)phenyl)-1-isobutyl-N-(4-(((1-propyl-1H-imidazol-5-yl)methyl)sulfinyl)phenyl)-1,2,3,4-tetrahydrobenzo[b]azocine-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/s1 Key: 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/s1 Key: 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−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Cenicriviroc (INN,^[1] code names TAK-652, TBR-652) is an experimental drug candidate for the treatment of HIV infection^[2] and in combination with Tropifexor for non-alcoholic steatohepatitis.^[3] It is being developed by Takeda and Tobira Therapeutics.

Cenicriviroc is an inhibitor of CCR2 and CCR5 receptors,^[4] 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.^[5] Additional Phase II clinical trials are underway.^[6]

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.^[7]

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.
^ https://clinicaltrials.gov/ct2/show/NCT03517540
^ 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.
^ CROI 2013: CCR5/CCR2 Inhibitor Cenicriviroc Has Both Anti-HIV and Anti-inflammatory Effects. Highleyman, Liz. HIVandHepatitis.com. 7 March 2013.

[INN-1] "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.

[2] 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.

[3] ttps://clinicaltrials.gov/ct2/show/NCT03517540

[4] 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.

[5] 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.

[6] "Tobira Therapeutics Initiates Phase 2b Trial of Cenicriviroc". The Body. July 5, 2011.

[7] CROI 2013: CCR5/CCR2 Inhibitor Cenicriviroc Has Both Anti-HIV and Anti-inflammatory Effects. Highleyman, Liz. HIVandHepatitis.com. 7 March 2013.

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See also

References