Leronlimab

Identification

Name
Leronlimab
Accession Number
DB05941
Description

Leronlimab, or PRO-140, is a human monoclonal antibody developed by CytoDyn.4 It was first described in the literature in 2001.1 This antibody binds to CCR5, which may be useful in treating HIV, cancers, and severely ill COVID-19 patients.2,3,4

Type
Biotech
Groups
Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
Not Available
Synonyms
  • Leronlimab
External IDs
  • PA14
  • PRO 140
  • PRO-140
  • PRO140
  • WHO 10751

Pharmacology

Pharmacology
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Indication

Leronlimab is currently being investigated for the treatment of a number of cancers3 and HIV.1

Recently leronlimab has begun a phase II clinical trial in severely ill COVID-19 patients.4 Preliminary data shows a reduction in the 'cytokine storm', particularly IL-6, as well as a normalization of the CD4/CD8 T-cell ratio.4 These results may mitigate immune mediate injury seen in severely ill COVID-19 patients.4

Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Leronlimab is a humanized monoclonal antibody that binds CCR5 being investigated for it's anti-HIV, immunomodulatory, and anti-cancer effects.1,3,4

Mechanism of action

CCR5 is a helical protein with multiple extracellular regions with adjacent G proteins.1,3 When a chemokine binds CCR5, the Gαβγ trimer phosphorylates GDP to GTP and Gα dissociates.3 Activated Gα activates adenylate cyclase, and increasing levels of cyclic AMP activate cytosolic protein kinase A.3 Further downstream effects of CCR5 signalling include activation of NF-κB and IL-6, as well as effects on cell proliferation, migration, and survival.3,4

HIV enters cells expressing CD4 and a fusion coreceptor such as CCR5 and CXCR4.1 Leronlimab is a monoclonal antibody which binds to multiple extracellular regions of the CCR5 receptor, preventing the entry of HIV into the cell.1

Leronlimab's blocking of CCR5 is being investigated in cancer treatment, for it's effect on the cell cycle and immuno-modulation.3

Leronlimab is also being investigated as a treatment for patients severely ill with COVID-19 due to it's effects on mitigating the cytokine storm and preventing immune-mediated injury.4

TargetActionsOrganism
UC-C chemokine receptor type 5
antagonist
Humans
Absorption

A 162mg subcutaneous dose reaches a Cmax of 6.1mg/L, with a Tmax of 32 hours, and an AUC of 24.4mg*day/L.2 A 324mg subcutaneous dose reaches a Cmax of 13.8mg/L, with a Tmax of 56 hours, and an AUC of 58.8mg*day/L.2

Volume of distribution

Data regarding the volume of distribution of leronlimab is not readily available.

Protein binding

Data regarding the protein binding of leronlimab is not readily available.

Metabolism

Data regarding the metabolism of leronlimab is not readily available. However, as a monoclonal antibody it is expected to be degraded to smaller proteins and amino acids by proteolytic enzymes.

Route of elimination

Data regarding the route of elimination of leronlimab is not readily available.

Half-life

The half life of a 162mg subcutaneous dose is 3.4 days while the half life of a 324mg subcutaneous dose is 3.7 days.2

Clearance

Data regarding the clearance of leronlimab is not readily available.

Adverse Effects
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Toxicity

Data regarding overdose of leronlimab is not readily available.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Leronlimab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Leronlimab.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Leronlimab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Leronlimab.
AlirocumabThe risk or severity of adverse effects can be increased when Leronlimab is combined with Alirocumab.
AnsuvimabThe risk or severity of adverse effects can be increased when Leronlimab is combined with Ansuvimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Leronlimab is combined with Anthrax immune globulin human.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Leronlimab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Leronlimab is combined with Antilymphocyte immunoglobulin (horse).
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Leronlimab.
Interactions
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Food Interactions
No interactions found.

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Chemical Identifiers

UNII
Y1J4NP8FF0
CAS number
674782-26-4

References

General References
  1. Trkola A, Ketas TJ, Nagashima KA, Zhao L, Cilliers T, Morris L, Moore JP, Maddon PJ, Olson WC: Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J Virol. 2001 Jan;75(2):579-88. [PubMed:11134270]
  2. Jacobson JM, Thompson MA, Lalezari JP, Saag MS, Zingman BS, D'Ambrosio P, Stambler N, Rotshteyn Y, Marozsan AJ, Maddon PJ, Morris SA, Olson WC: Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody. J Infect Dis. 2010 May 15;201(10):1481-7. doi: 10.1086/652190. [PubMed:20377413]
  3. Kranjc MK, Novak M, Pestell RG, Lah TT: Cytokine CCL5 and receptor CCR5 axis in glioblastoma multiforme. Radiol Oncol. 2019 Nov 20;53(4):397-406. doi: 10.2478/raon-2019-0057. [PubMed:31747383]
  4. CytoDyn: Treatment with CytoDyn's Leronlimab Indicates Significant Trend Toward Immunological Restoration in Severely Ill COVID-19 Patients [Link]
Wikipedia
PRO_140

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1) Infection1
2RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)2
2RecruitingTreatmentNonalcoholic Steatohepatitis (NASH)1
2RecruitingTreatmentSolid Tumor, Adult1
2Unknown StatusTreatmentGraft Versus Host Disease (GVHD)1
2WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections3
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
Receptor for a number of inflammatory CC-chemokines including MIP-1-alpha, MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a r...
Gene Name
CCR5
Uniprot ID
P51681
Uniprot Name
C-C chemokine receptor type 5
Molecular Weight
40523.645 Da
References
  1. Miao M, De Clercq E, Li G: Clinical significance of chemokine receptor antagonists. Expert Opin Drug Metab Toxicol. 2020 Jan;16(1):11-30. doi: 10.1080/17425255.2020.1711884. Epub 2020 Jan 17. [PubMed:31903790]
  2. Trkola A, Ketas TJ, Nagashima KA, Zhao L, Cilliers T, Morris L, Moore JP, Maddon PJ, Olson WC: Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J Virol. 2001 Jan;75(2):579-88. [PubMed:11134270]

Drug created on November 18, 2007 18:28 / Updated on February 21, 2021 18:51