Forodesine

Summary

Forodesine (CHEMBL218291) is an approved small molecule targeting PNP; indicated across 5 conditions including b-cell chronic lymphocytic leukemia and leukemia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 1 (PNP)
• Indications: 5 conditions
• Clinical trials: 8
• Chemistry: 266.25 Da · C11H14N4O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL218291
Name	Forodesine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	135409409
ChEBI	CHEBI:43362
Molecular formula	C11H14N4O4
Molecular weight	266.25
InChIKey	IWKXDMQDITUYRK-KUBHLMPHSA-N

SMILES: C1=C(C2=C(N1)C(=O)NC=N2)[C@H]3[C@@H]([C@@H]([C@H](N3)CO)O)O

IUPAC name: 7-[(2S,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one

Also known as: BCX-1777, Fodosine, Forodesina, Forodesine, Immucillin h, Mundesine, NSC-717904, immucillin-H, Immucillin-H, Immucillin H, FORODESINE, Forodesine (hydrochloride)

Parent form; salt/anhydrous children: CHEMBL550755, CHEMBL1213652

Patent coverage: 564 distinct patent families (1,563 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 1,500 (96%) of the total. 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
PNP	purine nucleoside phosphorylase	Inhibition	10.14	0%	P00491
	Plasmodium falciparum purine nucleoside phosphorylase		9.22

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Purine nucleoside phosphorylase, Purine nucleoside phosphorylase, Purine nucleoside phosphorylase, Purine nucleoside phosphorylase, Purine nucleoside phosphorylase.

Bioactivity

ChEMBL activities: 28 potent at pChembl ≥ 5 of 28 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P55859	10.64	Kd	0.02	nM	CHEMBL_ACT_12071664
P55859	10.64	Ki	0.02	nM	CHEMBL_ACT_19103825
P55859	10.64	Ki	0.02	nM	CHEMBL_ACT_356246
PNP	10.25	Ki	0.06	nM	CHEMBL_ACT_1077892
PNP	10.25	Ki	0.06	nM	CHEMBL_ACT_1089174
PNP	10.25	Ki	0.06	nM	CHEMBL_ACT_19103821
PNP	10.25	Ki	0.06	nM	CHEMBL_ACT_2391442
PNP	10.25	Ki	0.06	nM	CHEMBL_ACT_25995008
PNP	10.25	Kd	0.06	nM	CHEMBL_ACT_3563573
PNP	10.25	Ki	0.06	nM	CHEMBL_ACT_458580
PNP	10.24	Ki	0.06	nM	CHEMBL_ACT_2587846
PNP	10.22	IC50	0.06	nM	CHEMBL_ACT_24999857
PNP	10.14	Ki	0.07	nM	CHEMBL_ACT_356244
Q8T9Z7	9.22	Ki	0.6	nM	CHEMBL_ACT_19143417
Q8I3X4	9.07	Ki	0.86	nM	CHEMBL_ACT_25995028
Q8T9Z7	9.07	Ki	0.86	nM	CHEMBL_ACT_3563574
PNP	8.74	Ki	1.8	nM	CHEMBL_ACT_1772057
PNP	8.48	Ki	3.3	nM	CHEMBL_ACT_1077891
PNP	8.48	Ki	3.3	nM	CHEMBL_ACT_2587836
PNP	8.48	Ki	3.3	nM	CHEMBL_ACT_458579
PNP	8.46	IC50	3.5	nM	CHEMBL_ACT_1772056
PNP	7.96	Ki	11	nM	CHEMBL_ACT_2587870
Q8T9Z7	7.54	Ki	29	nM	CHEMBL_ACT_19143413
P55859	7.39	Ki	41	nM	CHEMBL_ACT_3119885
P9WP01	7.38	IC50	42	nM	CHEMBL_ACT_25532926
PNP	7.24	IC50	57	nM	CHEMBL_ACT_25532889
PNP	7	IC50	100	nM	CHEMBL_ACT_2667365
Q8T9Z7	6.99	IC50	103	nM	CHEMBL_ACT_25533218

Target pathways

Aggregated over 1 target gene(s): PNP.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
Neutrophil degranulation	1	PNP
Purine salvage	1	PNP
Purine catabolism	1	PNP
Defective PNP disrupts phosphorolysis of (deoxy)guanosine and (deoxy)inosine	1	PNP
Ribavirin ADME	1	PNP

Dominant GO biological processes

GO term	Targets
allantoin metabolic process	1
nucleobase-containing compound metabolic process	1
inosine catabolic process	1
deoxyinosine catabolic process	1
deoxyadenosine catabolic process	1
purine ribonucleoside salvage	1
IMP catabolic process	1
nicotinamide riboside catabolic process	1
immune response	1
nucleotide biosynthetic process	1
response to xenobiotic stimulus	1
positive regulation of interleukin-2 production	1
urate biosynthetic process	1
positive regulation of T cell proliferation	1
purine-containing compound salvage	1

Indications & clinical

Indications

5 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
B-cell chronic lymphocytic leukemia	2	MONDO:0004948	EFO:0000095
leukemia	2	MONDO:0005059	EFO:0000565
lymphoma	2	MONDO:0005062	EFO:0000574
primary cutaneous T-cell non-Hodgkin lymphoma	2	MONDO:0000607	EFO:0002913
B-cell acute lymphoblastic leukemia	1	MONDO:0004947	EFO:0000094

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE2	4
PHASE1/PHASE2	3
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00035022	PHASE1/PHASE2	COMPLETED	Study of Intravenous BCX-1777 in Relapsed or Refractory Aggressive T-Cell Leukemias or Lymphomas
NCT00095381	PHASE2	COMPLETED	Repeat-Dose of Forodesine Hydrochloride (BCX-1777) Infusion in Patients With Advanced T-Cell Leukemia
NCT00289549	PHASE2	COMPLETED	Study of Forodesine Hydrochloride in Patients With Advanced, Fludarabine-refractory Chronic Lymphocytic Leukemia (CLL)
NCT00289562	PHASE1/PHASE2	COMPLETED	Forodesine Hydrochloride (BCX-1777) for B-Cell Acute Lymphoblastic Leukemia
NCT00419081	PHASE2	TERMINATED	Study of Forodesine Hydrochloride in Patients With Relapsed/Refractory Precursor T-Lymphoblastic Leukemia/Lymphoma Who Have Failed Two or More Prior Treatment Regimens
NCT00501735	PHASE2	COMPLETED	Forodesine in the Treatment of Cutaneous T-Cell Lymphoma
NCT00742495	PHASE1/PHASE2	TERMINATED	Pharmacokinetic Study of Forodesine in Children With Relapsed or Refractory T-cell or B-cell Precursor Acute Lymphoblastic Leukaemia or T-cell Non- Hodgkin’s Lymphoma.
NCT00646165	PHASE1	TERMINATED	Trial of Forodesine in Patients With Relapsed B-cell Chronic Lymphocytic Leukemia

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.

9 molecules share ≥1 primary target. Top 9 by shared-target count:

Molecule	Source	Status	Shared targets
ACYCLOVIR	ChEMBL + PubChem	Phase 4 (approved)	PNP
CLADRIBINE	ChEMBL + PubChem	Phase 4 (approved)	PNP
GUANINE	ChEMBL	Phase 3	PNP
DEZAGUANINE	ChEMBL	Phase 2	PNP
GALIDESIVIR	ChEMBL	Phase 2	PNP
PELDESINE	ChEMBL	Phase 2	PNP
ULODESINE	ChEMBL	Phase 2	PNP
Adenosine	PubChem	Approved	PNP
Ribavirin	PubChem	Approved	PNP