Forodesine

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

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Name
Forodesine
Accession Number
DB06185  (DB03743)
Type
Small Molecule
Groups
Investigational
Description

Forodesine is a highly potent, orally active, rationally designed PNP inhibitor that has shown activity in preclinical studies with malignant cells and clinical utility against T-cell acute lymphoblastic leukemia and cutaneous T-cell lymphoma. Additional preliminary findings support its use for the management of some B-cell malignancies.

Structure
Thumb
Synonyms
  • (1S)-1,4-dideoxy-4-imino-(9-deazahypoxanthin-9-yl)-D-ribitol
  • 1,4-Dideoxy-4-aza-1-(S)-(9-deazahypoxanthin-9-yl)-D-ribitol
  • Forodesine
  • Immucillin H
  • Immucillin-H
External IDs
BCX-1777
Product Ingredients
IngredientUNIICASInChI Key
Forodesine hydrochloride6SN82Y9U73284490-13-7WEIAMZKHBCLFOG-QPAIBFMUSA-N
International/Other Brands
Fodosine / Mundesine
Categories
UNII
426X066ELK
CAS number
209799-67-7
Weight
Average: 266.2533
Monoisotopic: 266.101504956
Chemical Formula
C11H14N4O4
InChI Key
IWKXDMQDITUYRK-KUBHLMPHSA-N
InChI
InChI=1S/C11H14N4O4/c16-2-5-9(17)10(18)7(15-5)4-1-12-8-6(4)13-3-14-11(8)19/h1,3,5,7,9-10,12,15-18H,2H2,(H,13,14,19)/t5-,7+,9-,10+/m1/s1
IUPAC Name
7-[(2S,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidin-2-yl]-3H,4H,5H-pyrrolo[3,2-d]pyrimidin-4-one
SMILES
OC[C@H]1N[C@H]([C@H](O)[C@@H]1O)C1=CNC2=C1N=CNC2=O

Pharmacology

Indication

Investigated for use/treatment in lymphoma (non-hodgkin's) and leukemia (lymphoid).

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UPurine nucleoside phosphorylaseNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Galmarini CM: Drug evaluation: forodesine - PNP inhibitor for the treatment of leukemia, lymphoma and solid tumor. IDrugs. 2006 Oct;9(10):712-22. [PubMed:17016779]
External Links
KEGG Drug
D06596
PubChem Compound
444499
ChemSpider
392417
BindingDB
50195587
ChEBI
43362
ChEMBL
CHEMBL218291
HET
IMH
Wikipedia
Forodesine
PDB Entries
1b8o / 1g2o / 1nw4 / 1pf7 / 1rr6 / 1rt9 / 2ff1 / 2ff2 / 2oc4 / 2oc9
show 5 more

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMalignancies1
1CompletedTreatmentMalignant Lymphomas1
1CompletedTreatmentRecurrent or Refractory T/NK-cell Malignancies1
1TerminatedTreatmentB-Cell Chronic Lymphocytic Leukemia1
1, 2CompletedTreatmentB-cell Acute Lymphoblastic Leukemia1
1, 2CompletedTreatmentLeukemia, Lymphocytic / Malignant Lymphomas1
1, 2CompletedTreatmentMalignant Lymphomas1
1, 2CompletedTreatmentRecurrent or Refractory PTCL1
1, 2TerminatedTreatmentB-cell Precursor Acute Lymphoblastic Leukaemia / Relapsed or Refractory T-cell Acute Lymphoblastic Leukaemia / T-Cell Non-Hodgkin Lymphoma1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)2
2CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL)1
2CompletedTreatmentLeukemia, T-Cell1
2TerminatedTreatmentLeukemias / Malignant Lymphomas1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.11 mg/mLALOGPS
logP-1.8ALOGPS
logP-2.8ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)10.03ChemAxon
pKa (Strongest Basic)8.22ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area129.97 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity66.37 m3·mol-1ChemAxon
Polarizability25.81 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9784
Blood Brain Barrier-0.7642
Caco-2 permeable-0.8425
P-glycoprotein substrateSubstrate0.5108
P-glycoprotein inhibitor INon-inhibitor0.9882
P-glycoprotein inhibitor IINon-inhibitor0.9682
Renal organic cation transporterNon-inhibitor0.9062
CYP450 2C9 substrateNon-substrate0.8181
CYP450 2D6 substrateNon-substrate0.7955
CYP450 3A4 substrateNon-substrate0.5742
CYP450 1A2 substrateNon-inhibitor0.7907
CYP450 2C9 inhibitorNon-inhibitor0.9242
CYP450 2D6 inhibitorNon-inhibitor0.9001
CYP450 2C19 inhibitorNon-inhibitor0.9373
CYP450 3A4 inhibitorNon-inhibitor0.8658
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8575
Ames testNon AMES toxic0.7612
CarcinogenicityNon-carcinogens0.9209
BiodegradationNot ready biodegradable0.8571
Rat acute toxicity2.0847 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.992
hERG inhibition (predictor II)Non-inhibitor0.9018
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyrrolopyrimidines. These are compounds containing a pyrrolopyrimidine moiety, which consists of a pyrrole ring fused to a pyrimidine. Pyrrole is 5-membered ring consisting of four carbon atoms and one nitrogen atom. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrrolopyrimidines
Sub Class
Not Available
Direct Parent
Pyrrolopyrimidines
Alternative Parents
Pyrimidones / Aralkylamines / Substituted pyrroles / Vinylogous amides / Pyrrolidines / Heteroaromatic compounds / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Azacyclic compounds
show 4 more
Substituents
Pyrrolopyrimidine / Pyrimidone / Aralkylamine / Pyrimidine / Substituted pyrrole / Pyrrole / Pyrrolidine / Heteroaromatic compound / Vinylogous amide / 1,2-aminoalcohol
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
dihydroxypyrrolidine, pyrrolopyrimidine (CHEBI:43362)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Purine-nucleoside phosphorylase activity
Specific Function
The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine ...
Gene Name
PNP
Uniprot ID
P00491
Uniprot Name
Purine nucleoside phosphorylase
Molecular Weight
32117.69 Da
References
  1. Furman RR, Hoelzer D: Purine nucleoside phosphorylase inhibition as a novel therapeutic approach for B-cell lymphoid malignancies. Semin Oncol. 2007 Dec;34(6 Suppl 5):S29-34. [PubMed:18086344]
  2. Gore L, Stelljes M, Quinones R: Forodesine treatment and post-transplant graft-versus-host disease in two patients with acute leukemia: facilitation of graft-versus-leukemia effect? Semin Oncol. 2007 Dec;34(6 Suppl 5):S35-9. [PubMed:18086346]
  3. Gandhi V, Kilpatrick JM, Plunkett W, Ayres M, Harman L, Du M, Bantia S, Davisson J, Wierda WG, Faderl S, Kantarjian H, Thomas D: A proof-of-principle pharmacokinetic, pharmacodynamic, and clinical study with purine nucleoside phosphorylase inhibitor immucillin-H (BCX-1777, forodesine). Blood. 2005 Dec 15;106(13):4253-60. Epub 2005 Aug 30. [PubMed:16131572]

Drug created on March 19, 2008 10:16 / Updated on June 04, 2019 06:21