PLERIXAFOR OCTAHYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H54N8.8ClH
Molecular Weight	794.469
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of PLERIXAFOR OCTAHYDROCHLORIDE

Structure Search

SMILES

Cl.Cl.Cl.Cl.Cl.Cl.Cl.Cl.C(N1CCCNCCNCCCNCC1)C2=CC=C(CN3CCCNCCNCCCNCC3)C=C2

InChI

InChIKey=UEUPDYPUTTUXLJ-UHFFFAOYSA-N

InChI=1S/C28H54N8.8ClH/c1-9-29-15-17-31-13-3-21-35(23-19-33-11-1)25-27-5-7-28(8-6-27)26-36-22-4-14-32-18-16-30-10-2-12-34-20-24-36;;;;;;;;/h5-8,29-34H,1-4,9-26H2;8*1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C28H54N8
Molecular Weight	502.782
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022311s016lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/19161986

Plerixafor is a bicyclam molecule, which has been identified as a specific antagonist of CXCR4. It had originally been developed as an inhibitor of T-tropic human immunodeficiency virus, but later demonstrated to be an effective mobilizer of hematopoietic stem cells. Plerixafor was approved by FDA for autologous transplantation (in combination with granulocyte-colony stimulating factor) in patients with non-Hodgkin's lymphoma and multiple myeloma under the name Mozobil.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
C-X-C chemokine receptor type 4 5 Target ID: P61073 Gene ID: 7852.0 Gene Symbol: CXCR4 Target Organism: Homo sapiens (Human) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022311s016lbl.pdf	Antagonist 2737		44.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Non-Hodgkin's lymphoma 79 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022311s016lbl.pdf	Primary		Approved 8307	MOZOBIL Approved Use Mozobil (plerixafor) injection is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Launch Date 1.22929925E12
Multiple myeloma 153 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022311s016lbl.pdf	Primary		Approved 8307	MOZOBIL Approved Use Mozobil (plerixafor) injection is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Launch Date 1.22929925E12

C_max

Value	Dose	Co-administered	Analyte	Population
1029 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19135941	240 μg/kg bw single, subcutaneous dose: 240 μg/kg bw route of administration: Subcutaneous experiment type: SINGLE co-administered:		PLERIXAFOR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
5260 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19135941	240 μg/kg bw single, subcutaneous dose: 240 μg/kg bw route of administration: Subcutaneous experiment type: SINGLE co-administered:		PLERIXAFOR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19135941	240 μg/kg bw single, subcutaneous dose: 240 μg/kg bw route of administration: Subcutaneous experiment type: SINGLE co-administered:		PLERIXAFOR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
160 ug/kg/h multiple, intravenous Highest studied dose Dose: 160 ug/kg/h Route: intravenous Route: multiple Dose: 160 ug/kg/h Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	unhealthy, 40.2 years n = 3 Health Status: unhealthy Condition: HIV-1 Infection Age Group: 40.2 years Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	Disc. AE: Premature ventricular contractions... AEs leading to discontinuation/dose reduction: Premature ventricular contractions (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15385732
20 ug/kg/h multiple, intravenous Dose: 20 ug/kg/h Route: intravenous Route: multiple Dose: 20 ug/kg/h Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	unhealthy, 40.2 years n = 8 Health Status: unhealthy Condition: HIV-1 Infection Age Group: 40.2 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	Disc. AE: Hepatic enzyme increased, Orthostatic hypotension... AEs leading to discontinuation/dose reduction: Hepatic enzyme increased (1 patient) Orthostatic hypotension (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15385732
40 ug/kg/h multiple, intravenous Dose: 40 ug/kg/h Route: intravenous Route: multiple Dose: 40 ug/kg/h Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	unhealthy, 40.2 years n = 8 Health Status: unhealthy Condition: HIV-1 Infection Age Group: 40.2 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	Disc. AE: Ventricular ectopics... AEs leading to discontinuation/dose reduction: Ventricular ectopics (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15385732
5 ug/kg/h multiple, intravenous Dose: 5 ug/kg/h Route: intravenous Route: multiple Dose: 5 ug/kg/h Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	unhealthy, 40.2 years n = 7 Health Status: unhealthy Condition: HIV-1 Infection Age Group: 40.2 years Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	Disc. AE: Thrombocytopenia... AEs leading to discontinuation/dose reduction: Thrombocytopenia (serious, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15385732
80 ug/kg/h multiple, intravenous Dose: 80 ug/kg/h Route: intravenous Route: multiple Dose: 80 ug/kg/h Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	unhealthy, 40.2 years n = 5 Health Status: unhealthy Condition: HIV-1 Infection Age Group: 40.2 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/15385732	Disc. AE: Paresthesia... AEs leading to discontinuation/dose reduction: Paresthesia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15385732
160 ug/kg single, oral Dose: 160 ug/kg Route: oral Route: single Dose: 160 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10817726	healthy, >18 years n = 3 Health Status: healthy Age Group: >18 years Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/10817726	Sources: https://pubmed.ncbi.nlm.nih.gov/10817726
80 ug/kg single, intravenous Dose: 80 ug/kg Route: intravenous Route: single Dose: 80 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10817726	healthy, >18 years n = 12 Health Status: healthy Age Group: >18 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10817726	Other AEs: Diaphoresis... Other AEs: Diaphoresis (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/10817726
320 ug/kg single, subcutaneous Highest studied dose Dose: 320 ug/kg Route: subcutaneous Route: single Dose: 320 ug/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_MedR.pdf Page: p. 83	healthy, adult n = 10 Health Status: healthy Age Group: adult Population Size: 10 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_MedR.pdf Page: p. 83	Other AEs: Injection site erythema, Paresthesia... Other AEs: Injection site erythema Paresthesia Chest discomfort Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_MedR.pdf Page: p. 83
0.24 mg/kg 1 times / day multiple, subcutaneous Recommended Dose: 0.24 mg/kg, 1 times / day Route: subcutaneous Route: multiple Dose: 0.24 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_MedR.pdf Page: p.97	unhealthy, adult n = 72 Health Status: unhealthy Age Group: adult Population Size: 72 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_MedR.pdf Page: p.97	Disc. AE: Anxiety, Arrhythmia... AEs leading to discontinuation/dose reduction: Anxiety (1 patient) Arrhythmia (1 patient) Erythema (1 patient) Decreased appetite (1 patient) Eructation (1 patient) Liver function test abnormal (1 patient) Nausea (2 patients) Vomiting (2 patients) Postural hypotension (1 patient) Sinus tachycardia (1 patient) Staphylococcal bacteremia (1 patient) Insomnia (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_MedR.pdf Page: p.97

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1695 inducer 372	inhibitor 1789 inducer 97	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2A6 670 CYP2B6 770 CYP2C8 869 CYP2C19 1410 CYP3A4/5 261 P-gp 1401 CYP2E1 846 CYP4A9/11 34	CYP 252 P-gp 1491	CYP1A2 671 CYP2B6 521 CYP3A4/5 112 P-gp 252 CYP2C19 283

Drug as perpetrator

Target	Modality	Activity
P-gp 1588	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_ClinPharmR.pdf Page: 60, 104	inconclusive
P-gp 1588	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_ClinPharmR.pdf Page: 58, 104	inconclusive
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 9, 42, 80	no [IC50 >100 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 9, 42, 80	no [IC50 >100 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 9, 42, 80	no [IC50 >100 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 9, 42, 80	no [IC50 >100 uM]
CYP2E1 929	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_PharmR_P1.pdf Page: 55.0	no [IC50 >100 uM]
CYP3A4/5 314	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 9, 42, 80	no [IC50 >100 uM]
CYP4A9/11 34	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_PharmR_P1.pdf Page: 55.0	no [IC50 >100 uM]
CYP1A2 1620	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 80.0	no
CYP2A6 702	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022311s022lbl.pdf Page: 11.0	no
CYP2B6 946	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_ClinPharmR.pdf Page: 59.0	no
CYP2B6 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022311s022lbl.pdf Page: 11.0	no
CYP2C19 1484	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 80.0	no
CYP2C8 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022311s022lbl.pdf Page: 11.0	no
CYP2C9 1747	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 80.0	no
CYP2D6 1826	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 80.0	no
CYP3A4/5 314	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 80.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1491	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_ClinPharmR.pdf Page: 58, 104	inconclusive
CYP 252	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_ClinPharmR.pdf Page: 15, 102	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022311s000_PharmR.pdf Page: 17, 34, 40

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:125354	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:125354
ChemicalBook	CB11011749	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB11011749
MolPort	MolPort-009-019-417	https://www.molport.com/shop/molecule-link/MolPort-009-019-417
Selleck Chemicals	plerixafor	http://www.selleckchem.com/products/plerixafor.html
ZINC	ZINC000022443609	http://zinc15.docking.org/substances/ZINC000022443609
eMolecules	6842643	https://www.emolecules.com/cgi-bin/more?vid=6842643

PubMed

Title	Date	PubMed
Marked increase in anti-HIV activity, as well as inhibitory activity against HIV entry mediated by CXCR4, linked to enhancement of the binding ability of tachyplesin analogs to CXCR4.	1999 Mar 20	10195751
A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity.	1999 May 11	10318947
Viral entry through CXCR4 is a pathogenic factor and therapeutic target in human immunodeficiency virus type 1 disease.	2000 Jan	10590105
Anti-human immunodeficiency virus activity of novel aminoglycoside-arginine conjugates at early stages of infection.	2000 May 1	10791873
Strong in vitro synergy between the fusion inhibitor T-20 and the CXCR4 blocker AMD-3100.	2000 Oct 1	11103038
Viral entry as the primary target for the anti-HIV activity of chicoric acid and its tetra-acetyl esters.	2000 Sep	10953059
Inhibition of HIV infection by CXCR4 and CCR5 chemokine receptor antagonists.	2001	11594685
Pharmacological evidence for complex and multiple site interaction of CXCR4 with SDF-1alpha: implications for development of selective CXCR4 antagonists.	2001 Aug 1	11470148
Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4.	2002 Sep 11	12220670
Potent and selective inhibition of HIV and SIV by prostratin interacting with viral entry.	2003 Nov	14968938
Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue.	2004 Apr 19	15078900
Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist.	2004 Dec	15542651
New bicyclam-GalCer analogue conjugates: synthesis and in vitro anti-HIV activity.	2004 Jan 19	14698189
Theaflavin derivatives in black tea and catechin derivatives in green tea inhibit HIV-1 entry by targeting gp41.	2005 May 25	15823507
The Role of Plerixafor (AMD3100) in Mobilizing Hematopoietic Progenitor Cells in Patients with Hematologic Malignancies.	2006 Jan 1	18632442
CXCR4 inhibition synergizes with cytotoxic chemotherapy in gliomas.	2006 Nov 15	17121897
Plerixafor: AMD 3100, AMD3100, JM 3100, SDZ SID 791.	2007	17324009
CXCR4 chemokine receptor signaling mediates pain hypersensitivity in association with antiretroviral toxic neuropathy.	2007 Jul	17292584
Stromal cell-derived factor-1 induces matrix metalloprotease-13 expression in human chondrocytes.	2007 Sep	17550983
Microenvironmental considerations in the application of human mesenchymal stem cells in regenerative therapies.	2008 Dec	19707450
17beta-estradiol promotes breast cancer cell proliferation-inducing stromal cell-derived factor-1-mediated epidermal growth factor receptor transactivation: reversal by gefitinib pretreatment.	2008 Jan	17959712
Potent synergistic anti-human immunodeficiency virus (HIV) effects using combinations of the CCR5 inhibitor aplaviroc with other anti-HIV drugs.	2008 Jun	18378711
A novel CXCR4 antagonist for hematopoietic stem cell mobilization.	2008 Nov	18922110
Bis-14-membered ring diketal diamines: synthesis and evaluation of their anti-HIV and anti-tumoral activities.	2009 Aug	19356827
Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF and plerixafor (AMD3100): an institutional experience.	2009 Jun	19182831
[Mobilisation of haematopoietic stem cells with plerixafor--secondary publication].	2009 Nov 2	19887056
Advances in mobilization for the optimization of autologous stem cell transplantation.	2009 Sep	19603345
Plerixafor (AMD3100) and granulocyte colony-stimulating factor (G-CSF) mobilize different CD34+ cell populations based on global gene and microRNA expression signatures.	2009 Sep 17	19602709
Binding of multivalent anionic porphyrins to V3 loop fragments of an HIV-1 envelope and their antiviral activity.	2010 Apr 1	20112333
Peripheral blood stem cell mobilization tactics.	2010 Jan	19996324
Safety and efficacy assessment of plerixafor in patients with multiple myeloma proven or predicted to be poor mobilizers, including assessment of tumor cell mobilization.	2010 Jan	19543330
Expression and function of CXCL12/CXCR4 in rat urinary bladder with cyclophosphamide-induced cystitis.	2010 Mar	20032115

Patents

Sample Use Guides

In Vivo Use Guide

Begin treatment with plerixafor (Mozobil) after the patient has received G-CSF once daily for four days. The recommended dose of plerixafor by subcutaneous injection is based on body weight: 20 mg fixed dose or 0.24 mg/kg of body weight for patients weighing ≤83 kg; 0.24 mg/kg of body weight for patients weighing >83 kg. Administer by subcutaneous injection approximately 11 hours prior to initiation of apheresis.

Route of Administration: Other

In Vitro Use Guide

Human colorectal cancer cell line SW480 was treated with plerixafor at different final concentrations (10, 100, 1000 ng/ml) for 2h. Then, CXCL12 was added daily at 20 ng/mL. MTT assays were performed after 24, 48 and 72 h of plerixafor treatment. Cell viability was significantly suppressed by the drug in a dose-dependent manner. The drug (100 and 1000 ng/mL) significantly inhibited the invasion ability of SW480 cells.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 23:53:48 UTC 2022` Edited by `admin` on `Fri Dec 16 23:53:48 UTC 2022`
Record UNII	OD49913540
Record Status	`Validated (UNII)`
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Name

Type

Language

PLERIXAFOR OCTAHYDROCHLORIDE

Common Name

English

SID 791

Code

English

PLERIXAFOR HYDROCHLORIDE

Common Name

English

Plerixafor octahydrochloride [WHO-DD]

Common Name

English

MOZOBIL

Common Name

English

AMD 3100

Code

English

PLERIXAFOR OCTAHYDROCHLORIDE [MI]

Common Name

English

JM 3100

Code

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/04/227