MOTOLIMOD

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H34N4O2
Molecular Weight	458.5952
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCN(CCC)C(=O)C1=CC2=C(C=C(C=C2)C3=CC=C(C=C3)C(=O)N4CCCC4)N=C(N)C1

InChI

InChIKey=QSPOQCXMGPDIHI-UHFFFAOYSA-N

InChI=1S/C28H34N4O2/c1-3-13-31(14-4-2)28(34)24-17-23-12-11-22(18-25(23)30-26(29)19-24)20-7-9-21(10-8-20)27(33)32-15-5-6-16-32/h7-12,17-18H,3-6,13-16,19H2,1-2H3,(H2,29,30)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28453702 | https://www.ncbi.nlm.nih.gov/pubmed/27810904 | https://clinicaltrials.gov/ct2/show/NCT01289210

Motolimod (VTX-2337) is a small molecule, selective Toll-like receptor (TLR) 8 agonist has been used in trials studying phase II for the treatment of peritoneal carcinoma, Ovarian Cancer, Fallopian Tube Cancer, B-cell lymphoma, squamous cell carcinoma of the head and neck among others. Motolimod is designed to mobilize a patient's immune system by directly activating myeloid dendritic cells, monocytes, and natural killer cells. This activation results in the production of a high level of mediators known to orchestrate the integration of both the innate and adaptive anti-tumor responses to a number of cancers.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Toll-like receptor 8 4 Target ID: Q9NR97 Gene ID: 51311.0 Gene Symbol: TLR8 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/22128302	Agonist 2752		100.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Head and neck squamous cell carcinoma 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27810904	Primary	Phase II 1147	Unknown Approved Use Unknown
Ovarian cancer 160 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28453702	Primary	Phase II 1147	Unknown Approved Use Unknown
Fallopian tube cancer 17 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28453702	Primary	Phase II 1147	Unknown Approved Use Unknown
Primary peritoneal cancer 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28453702	Primary	Phase II 1147	Unknown Approved Use Unknown
Low-grade B-cell lymphoma 1 Sources: https://clinicaltrials.gov/ct2/show/NCT01289210	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
23.03 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24807889	3.9 mg/m² single, subcutaneous dose: 3.9 mg/m² route of administration: Subcutaneous experiment type: SINGLE co-administered:		MOTOLIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
77.83 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24807889	3.9 mg/m² single, subcutaneous dose: 3.9 mg/m² route of administration: Subcutaneous experiment type: SINGLE co-administered:		MOTOLIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.55 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24807889	3.9 mg/m² single, subcutaneous dose: 3.9 mg/m² route of administration: Subcutaneous experiment type: SINGLE co-administered:		MOTOLIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003AP4	https://www.1pchem.com/search?query=1P003AP4
AChemBlock	L13490	http://www.achemblock.com/catalogsearch/result/?q=L13490
Ambeed	A388121	http://www.ambeed.com/search/Search.html?keyword=A388121
Angene	AGN-PC-0W0RPY	http://www.angenechemical.com/productshow/AGN-PC-0W0RPY.html
ApexBio Technology	B5996	https://www.apexbt.com/catalogsearch/result/?q=B5996
AstaTech	42300	http://astatechinc.com/CPSResult.php?CRNO=42300
Axon MedChem	2783	https://www.axonmedchem.com/product/2783
BLD Pharm	BD300982	http://www.bldpharm.com/search/Search.html?keyword=BD300982
Chem Scene	CS-4309	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4309
ChemShuttle	140528	https://www.chemshuttle.com/catalogsearch/result/?q=140528
eMolecules	56747961	https://orderbb.emolecules.com/search/#?query=56747961
Excenen	EX-A1102	http://www.excenen.com/searchresultlist.php?id=EX-A1102
KeyOrganics	AS-74258	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74258
mcule	MCULE-1697155251	https://mcule.com/MCULE-1697155251/
MedChem Express	HY-13773	https://www.medchemexpress.com/search.html?q=HY-13773&ft=&fa=&fp=
Molnova	M17666	https://www.molnova.com/en/serch-list.html?keywords=M17666
MolPort	MolPort-039-136-930	https://www.molport.com/shop/molecule-link/MolPort-039-136-930
MuseChem	I005515	https://www.musechem.com/product/I005515.html
Selleck Chemicals	S7161	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7161
ShangHai Biochempartner	BCP16667	http://www.biochempartner.com/search_BCP16667
TargetMol	T6898	https://www.targetmol.com/search?keyword=T6898

PubMed

Title	Date	PubMed
A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study.	2017-05-01	28453702
Motolimod effectively drives immune activation in advanced cancer patients.	2016-05	27467937
Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity.	2016	26928328
Late-Stage Cancer Patients Remain Highly Responsive to Immune Activation by the Selective TLR8 Agonist Motolimod (VTX-2337).	2015-12-15	26152744
VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC.	2012-01-15	22128302

Patents

Sample Use Guides

In Vivo Use Guide

Doses of motolimod (2.5, 3.0, or 3.5 mg/m2) were given on days 1, 8, and 15, in combination with fixed weekly doses of cetuximab in 28-day cycles Low Grade B Cell Lymphoma: sadiation on Day 1. On Day 2, VTX-2337 (MOTOLIMOD) 3.0mg/m2 is administered intratumorally, followed by radiation. VTX-2337 3.0mg/m2 is then given weekly for 3 weeks in a 4 week cycle over 3 cycles.

Route of Administration: Other

In Vitro Use Guide

VTX-2337 selectively activates TLR8 with an EC50 of about 100 nmol/L and stimulates production of TNFα and interleukin (IL)-12 from monocytes and myeloid dendritic cells (mDC). VTX-2337 (800 nmol/L) stimulates IFNγ production from NK cells and increases the cytotoxicity of NK cells against K562 and augment antibody-dependent cell-mediated cytotoxicity (ADCC) by rituximab and trastuzumab.

Name

Type

Language

motolimod [INN]

Preferred Name

English

MOTOLIMOD

Official Name

English

3H-1-BENZAZEPINE-4-CARBOXAMIDE, 2-AMINO-N,N-DIPROPYL-8-(4-(1-PYRROLIDINYLCARBONYL)PHENYL)-

Systematic Name

English

VTX-378

Code

English

MOTOLIMOD [USAN]

Common Name

English

Motolimod [WHO-DD]

Common Name

English

VTX-2337

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C2139