Agatolimod

Summary

Agatolimod (CHEMBL2103792) is a phase-3 clinical-stage oligonucleotide targeting TLR9; indicated across 1 condition including malaria.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Oligonucleotide
• Targets: 1 (TLR9)
• Indications: 1 condition
• Clinical trials: 10
• Chemistry: 7698 Da · C236H303N70O133P23S23

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2103792
Name	Agatolimod
Type	Oligonucleotide
Max phase	3
FDA approved	no
PubChem CID	70687253
Molecular formula	C236H303N70O133P23S23
Molecular weight	7698
InChIKey	OKYYOKGIPDRZJA-CPSXWDTOSA-N

SMILES: CC1=CN(C(=O)NC1=O)[C@H]2C[C@@H]([C@H](O2)COP(=S)(O)O[C@H]3C[C@@H](O[C@@H]3COP(=S)(O)O[C@H]4C[C@@H](O[C@@H]4COP(=S)(O)O[C@H]5C[C@@H](O[C@@H]5COP(=S)(O)O[C@H]6C[C@@H](O[C@@H]6COP(=S)(O)O[C@H]7C[C@@H](O[C@@H]7COP(=S)(O)O[C@H]8C[C@@H](O[C@@H]8COP(=S)(O)O[C@H]9C[C@@H](O[C@@H]9COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1COP(=S)(O)O[C@H]1C[C@@H](O[C@@H]1CO)N1C=C(C(=O)NC1=O)C)N1C=C(C(=O)NC1=O)C)N1C=NC2=C1N=C(NC2=O)N)N1C=CC(=NC1=O)N)N1C=C(C(=O)NC1=O)C)N1C=NC2=C1N=C(NC2=O)N)N1C=C(C(=O)NC1=O)C)N1C=C(C(=O)NC1=O)C)N1C=C(C(=O)NC1=O)C)N1C=C(C(=O)NC1=O)C)N1C=NC2=C1N=C(NC2=O)N)N1C=CC(=NC1=O)N)N1C=C(C(=O)NC1=O)C)N1C=NC2=C1N=C(NC2=O)N)N1C=C(C(=O)NC1=O)C)N1C=C(C(=O)NC1=O)C)N1C=C(C(=O)NC1=O)C)N1C=C(C(=O)NC1=O)C)N1C=NC2=C1N=C(NC2=O)N)N1C=CC(=NC1=O)N)N1C=C(C(=O)NC1=O)C)N1C=NC2=C1N=C(NC2=O)N)N1C=CC(=NC1=O)N)O

IUPAC name: 1-[(2R,4S,5R)-5-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[hydroxy-[(2R,3S,5R)-2-[[hydroxy-[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione

Also known as: Agatolimod, Cpg-10104, PF-3512676, Pf-3512676 free acid, AGATOLIMOD

Parent form; salt/anhydrous children: CHEMBL2103793

Patent coverage: 326 distinct patent families (848 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
TLR9	TLR9	Agonist		0.2%	Q9NR96

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 1 target gene(s): TLR9.

Top Reactome pathways

7 total, by targets touching each:

Pathway	Targets	Genes
PI3K Cascade	1	TLR9
Trafficking and processing of endosomal TLR	1	TLR9
Toll Like Receptor 9 (TLR9) Cascade	1	TLR9
Potential therapeutics for SARS	1	TLR9
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling	1	TLR9
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	TLR9
MyD88 dependent cascade initiated on endosome	1	TLR9

Dominant GO biological processes

GO term	Targets
microglial cell activation	1
toll-like receptor signaling pathway	1
positive regulation of immunoglobulin production	1
regulation of dendritic cell cytokine production	1
MyD88-dependent toll-like receptor signaling pathway	1
canonical NF-kappaB signal transduction	1
male gonad development	1
positive regulation of autophagy	1
positive regulation of gene expression	1
maintenance of gastrointestinal epithelium	1
positive regulation of B cell proliferation	1
detection of molecule of bacterial origin	1
positive regulation of chemokine production	1
positive regulation of granulocyte macrophage colony-stimulating factor production	1
positive regulation of interferon-alpha production	1

Indications & clinical

Indications

1 disease in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
malaria	1	MONDO:0005136	EFO:0001068

Clinical trials

Total trials: 10.

Phase distribution

Phase	Trials
PHASE2	7
PHASE3	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00254891	PHASE3	TERMINATED	Trial of Paclitaxel/Carboplatin + PF-3512676 vs Paclitaxel/Carboplatin Alone in Patients With Advanced Non-Small Cell Lung Cancer
NCT00254904	PHASE3	TERMINATED	Randomized Trial of Gemcitabine/Cisplatin + PF-3512676 vs Gemcitabine/Cisplatin Alone in Patients With Advanced NSCLC
NCT00043368	PHASE2	COMPLETED	PF-3512676 (CPG 7909) Injection For Patients Who Completed An Oncology Study Using PF-3512676 (CPG 7909)
NCT00043420	PHASE1/PHASE2	COMPLETED	CPG 7909 in Patients With Cutaneous T-Cell Lymphoma
NCT00313768	PHASE2	TERMINATED	Randomized Ph 2 Trial Of Paclitaxel/Carboplatin /Bevacizumab + PF-3512676 And P/C/B Alone In Advanced Nonsquamous NSCLC
NCT00321308	PHASE2	TERMINATED	Trial of Pemetrexed With or Without PF-3512676 in Advanced Non-Small Cell Lung Cancer
NCT00321815	PHASE2	COMPLETED	Trial Of Erlotinib With Or Without PF-3512676 In Advanced Non Small Cell Lung Cancer
NCT00471159	PHASE2	WITHDRAWN	A Study Of Docetaxel Or Docetaxel Plus PF-3512676 To Treat Patients With Advanced Breast Cancer.
NCT00490529	PHASE2	COMPLETED	Phase 1-2 of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL
NCT00880581	PHASE2	COMPLETED	A Phase 2 Intratumoral Injection PF-3512676 Plus Local Radiation in Low-Grade B-Cell Lymphomas

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

6 molecules share ≥1 primary target. Top 6 by shared-target count:

Molecule	Source	Status	Shared targets
HYDROXYCHLOROQUINE	ChEMBL + PubChem	Phase 4 (approved)	TLR9
CURCUMIN	ChEMBL	Phase 3	TLR9
THIMEROSAL	ChEMBL	Phase 3	TLR9
AFIMETORAN	ChEMBL	Phase 2	TLR9
MHV-370	ChEMBL	Phase 2	TLR9
Chloroquine	PubChem	Approved	TLR9