PRO 140

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PRO 140 ^?
Monoclonal antibody
Source	Humanized
Target	CCR5
Clinical data
Pregnancy cat.	?
Legal status	investigational
Identifiers
ATC code	None
NIAID ChemDB	AIDSNO:088103
Chemical data
Formula	?
Y(what is this?) (verify)

PRO 140 is a humanized monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human immune system. It is being investigated as a potential therapy in the treatment of HIV infection.^[1]

The United States Food and Drug Administration has designated PRO 140 for fast-track approval.^[2] In February 2008, the drug entered Phase 2 clinical trials.^[3]

Contents

1 Development
2 Mechanism of action
3 See also
4 External links
5 References

Development

PRO 140 is being developed by Progenics Pharmaceuticals. In May 2007, they announced results from the phase I clinical trial of the drug. The researchers said the results demonstrated "potent, rapid, prolonged, dose-dependent, highly significant antiviral activity" for PRO 140. Participants in the highest dosing group received 5 mg/kg and showed an average viral load decrease of -1.83 log₁₀. On average, reductions of greater than -1 log₁₀ copies/ml were maintained for between two and three weeks, from only a single dose of the drug.^[4] The largest individual HIV RNA reductions ranged up to -2.5 log₁₀ among patients receiving both the 2 and 5 mg/kg doses.^[5]

Mechanism of action

PRO 140 functions as an entry inhibitor.^[6]^[7] PRO 140 binds to the CCR5 receptor, and interferes with HIV's ability to enter the cell. Unlike other entry inhibitors, PRO 140 is a monoclonal antibody. As such, it must be injected to be effective. However, once inside the body, PRO 140 binds to CCR5 for >60 days,^[1] which may allow for dosing as infrequently as every other week.^[8]^[9]

External links

Animation of PRO 140 mechanism

References

^ ^a ^b Progenics Pharmaceuticals' HIV Drug, PRO 140, Receives FDA Fast-Track Designation. Press release, 22 Feb 2006. Progenics Pharmaceuticals.
^ Brian Lawler. Progenics' Intriguing Study Results. The Motley Fool. 2 May 2007.
^ "Phase 2 clinical trials started on PRO 140". AIDS Patient Care STDS 22 (2): 159–60. February 2008. doi:10.1089/apc.2008.9960. PMID 18273941.
^ Derek Thaczuk. ICAAC: Phase 1 study provides `proof of concept` for PRO 140, a monoclonal CCR5 antibody. AIDSmap.com. 21 Sept 2007.
^ Liz Highleyman. Monoclonal Antibody CCR5 Inhibitor PRO 140 Produces Long-lasting HIV Suppression in Single-dose Study. 28 Sept 2007. HIVandHepatitis.com
^ Biswas P, Tambussi G, Lazzarin A (2007). "Access denied? The status of co-receptor inhibition to counter HIV entry". Expert Opin Pharmacother 8 (7): 923–33. doi:10.1517/14656566.8.7.923. PMID 17472538. http://www.expertopin.com/doi/abs/10.1517/14656566.8.7.923.
^ Pugach P, Ketas TJ, Michael E, Moore JP (August 2008). "Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors". Virology 377 (2): 401–7. doi:10.1016/j.virol.2008.04.032. PMC 2528836. PMID 18519143. http://linkinghub.elsevier.com/retrieve/pii/S0042-6822(08)00272-9.
^ PRO 140. Progenics Pharmaceuticals.
^ Tim Horn. Single-Dose PRO 140 Has Lasting Effects. 21 Sept 2007. POZ.com.

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

Entry/fusion inhibitors
(Discovery & development)

gp41 (Enfuvirtide)
CCR5 (Maraviroc
Vicriviroc^†, Cenicriviroc^†, PRO 140^†)
CD4 (Ibalizumab^†)

Reverse-transcriptase
inhibitors (RTIs)

Nucleoside & Nucleotide (NRTI)	Nucleoside analogues/NARTIs: Abacavir (ABC)°^# Emtricitabine (FTC)°^# Lamivudine (3TC)°^# Didanosine (ddI)^# Zidovudine (AZT)^# Apricitabine^† Stampidine^† Elvucitabine^† Racivir^† Amdoxovir^† Stavudine (d4T)^# Zalcitabine (ddC)^◊ Festinavir^† Nucleotide analogues/NtRTIs: Tenofovir°^# GS 7340

Non-Nucleoside (NNRTI) (Discovery & development)	(1^st generation) Efavirenz°^# Nevirapine^# Loviride^◊ Delavirdine^◊ (2^nd generation) diarylpyrimidines (Etravirine Rilpivirine) Lersivirine^†

Integrase inhibitors

Maturation inhibitors

Bevirimat^†
Vivecon^†

Protease Inhibitors (PI)
(Discovery and development)

1^st generation	Fosamprenavir° Lopinavir°^# Nelfinavir^# Ritonavir^# Saquinavir^# Amprenavir^◊ Indinavir^◊^#

2^nd generation	Atazanavir° Darunavir Tipranavir

Combined formulations

Experimental agents

Uncoating inhibitors	TRIM5alpha (gene)

Transcription inhibitors	Tat antagonists

Translation inhibitors	Trichosanthin

Other	Abzyme Calanolide A Ceragenin Cyanovirin-N Diarylpyrimidines Epigallocatechin gallate (EGCG) Foscarnet Griffithsin Hydroxycarbamide Miltefosine Portmanteau inhibitors Seliciclib^† Synergistic enhancers Tre recombinase Zinc finger protein transcription factor KP-1461^† Cobicistat^†

Failed agents	Dexelvucitabine Capravirine Emivirine Lodenosine Atevirdine Brecanavir Aplaviroc

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

°DHHS preferred first-line agent. ^◊Formerly or rarely used agent.

M: VIR

virs(prot)/clss

cutn/syst (hppv/hiva, infl/zost/zoon)/epon

drugJ(dnaa, rnaa, rtva, vacc)

Monoclonal antibodies for the immune system

Immune system ("-l(i[m])-")

Human ("-limu-")	immunosuppression: Adalimumab Atorolimumab Brodalumab Carlumab Fresolimumab Golimumab Lerdelimumab Mavrilimumab Metelimumab Morolimumab Namilumab Oxelumab Sarilumab Sifalimumab Tabalumab Urelumab immune activation: Ipilimumab Tremelimumab other: Bertilimumab Zanolimumab

Mouse ("-limo-")	Afelimomab Elsilimomab Faralimomab Gavilimomab Inolimomab Maslimomab Nerelimomab Odulimomab Telimomab aritox Vepalimomab Zolimomab aritox

Chimeric ("-lixi-")	Basiliximab Clenoliximab Galiximab Gomiliximab Infliximab Keliximab Lumiliximab Priliximab Teneliximab Vapaliximab

Humanized ("-lizu-")	immunosuppressive: Aselizumab Apolizumab Benralizumab^† Cedelizumab Certolizumab pegol Daclizumab Eculizumab Efalizumab Epratuzumab Erlizumab Etrolizumab Fontolizumab Itolizumab Mepolizumab Mogamulizumab Natalizumab Ocrelizumab Omalizumab Ozoralizumab Pascolizumab Pateclizumab Pexelizumab PRO 140^† Reslizumab Rontalizumab Rovelizumab Ruplizumab Samalizumab Siplizumab Talizumab Teplizumab Tocilizumab Toralizumab Tregalizumab Vatelizumab Vedolizumab Visilizumab TGN1412^§ non-immunosuppressive: Ibalizumab^†

Chimeric + humanized ("-lixizu-")	Otelixizumab

Interleukin ("-k(i[n])-")

Human ("-kinu-")	Briakinumab Canakinumab Fezakinumab Secukinumab Sirukumab Tralokinumab Ustekinumab

Humanized ("-kizu-", "-kinzu-")	Anrukinzumab Enokizumab Gevokizumab Ixekizumab Lebrikizumab Olokizumab

Inflammatory lesions ("-les-")

Mouse ("-leso-")	Besilesomab Fanolesomab^‡ Lemalesomab Sulesomab

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

M: LMC

cell/phys/auag/auab/comp, igrc

imdf/ipig/hyps/tumr

proc, drug(L3/4)

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