Laromustine

Identification

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Name
Laromustine
Accession Number
DB05817  (DB12324)
Type
Small Molecule
Groups
Investigational
Description

VNP40101M is a novel alkylating agent that has been used in trials studying the treatment of Leukemia, Lymphoma, Lung Cancer, Small Intestine Cancer, and Myelodysplastic Syndromes, among others.

Structure
Thumb
Synonyms
  • Cloretazine
  • Onrigin
External IDs
101M / VNP 40101M / VNP-40101M / VNP40101M
International/Other Brands
Cloretazine
Categories
UNII
14J2G0U3NQ
CAS number
173424-77-6
Weight
Average: 307.775
Monoisotopic: 307.00633966
Chemical Formula
C6H14ClN3O5S2
InChI Key
PVCULFYROUOVGJ-UHFFFAOYSA-N
InChI
InChI=1S/C6H14ClN3O5S2/c1-8-6(11)10(17(3,14)15)9(5-4-7)16(2,12)13/h4-5H2,1-3H3,(H,8,11)
IUPAC Name
3-[N-(2-chloroethyl)methanesulfonamido]-3-methanesulfonyl-1-methylurea
SMILES
CNC(=O)N(N(CCCl)S(C)(=O)=O)S(C)(=O)=O

Pharmacology

Indication

Investigated for use/treatment in brain cancer, cancer/tumors (unspecified), colorectal cancer, leukemia (lymphoid), leukemia (myeloid), lung cancer, myelodysplastic syndrome, pediatric indications, and solid tumors.

Pharmacodynamics
Not Available
Mechanism of action

VNP40101M is a small molecule that works by damaging DNA. It releases the DNA chloroethylating agent 90CE after entering the blood stream. 90CE chloroethylates the O6 position of guanine residues, ultimately resulting in an interstrand DNA cross-link. Interstrand DNA cross-links are difficult to repair and are toxic to cells. VNP40101M demonstrates a broad spectrum of anticancer activity in preclinical studies, including activity in selected cell lines resistant to other alkylating agents such as BCNU, cyclophosphamide and melphalan. In preclinical studies, Cloretazine (VNP40101M) has been combined with other anticancer agents such as cytarabine (Ara-C). In addition, Cloretazine (VNP40101M) or its metabolite, has been shown to be capable of crossing the blood brain barrier in preclinical models.

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
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Giles F, Rizzieri D, Karp J, Vey N, Ravandi F, Faderl S, Khan KD, Verhoef G, Wijermans P, Advani A, Roboz G, Kantarjian H, Bilgrami SF, Ferrant A, Daenen SM, Karsten V, Cahill A, Albitar M, Mufti G, O'Brien S: Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. J Clin Oncol. 2007 Jan 1;25(1):25-31. Epub 2006 Dec 4. [PubMed:17146105]
External Links
PubChem Compound
3081349
PubChem Substance
175427039
ChemSpider
2338969
ChEMBL
CHEMBL167691

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentLeukemias1
1CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
1CompletedTreatmentLeukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms1
1CompletedTreatmentMalignancies, Hematologic1
1CompletedTreatmentMalignant Lymphomas / Small Intestine Cancer / Unspecified Adult Solid Tumor, Protocol Specific2
1TerminatedTreatmentBrain and Central Nervous System Tumors1
1, 2CompletedTreatmentLeukemias1
1, 2CompletedTreatmentLeukemias / Malignant Lymphomas1
1, 2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes (MDS)1
2CompletedTreatmentLeukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms1
2CompletedTreatmentLung Cancers1
2Unknown StatusTreatmentLeukemias1
3CompletedTreatmentLeukemias1

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 Solubility0.736 mg/mLALOGPS
logP-0.01ALOGPS
logP-1.9ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)12.87ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area103.86 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity61.91 m3·mol-1ChemAxon
Polarizability26.65 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8559
Blood Brain Barrier+0.8044
Caco-2 permeable-0.6019
P-glycoprotein substrateNon-substrate0.6696
P-glycoprotein inhibitor INon-inhibitor0.8511
P-glycoprotein inhibitor IINon-inhibitor0.9551
Renal organic cation transporterNon-inhibitor0.8851
CYP450 2C9 substrateNon-substrate0.5
CYP450 2D6 substrateNon-substrate0.6957
CYP450 3A4 substrateNon-substrate0.5549
CYP450 1A2 substrateNon-inhibitor0.8237
CYP450 2C9 inhibitorNon-inhibitor0.6915
CYP450 2D6 inhibitorNon-inhibitor0.8751
CYP450 2C19 inhibitorNon-inhibitor0.6605
CYP450 3A4 inhibitorNon-inhibitor0.9463
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9028
Ames testAMES toxic0.6094
CarcinogenicityNon-carcinogens0.5844
BiodegradationNot ready biodegradable0.7946
Rat acute toxicity3.0136 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7836
hERG inhibition (predictor II)Non-inhibitor0.9204
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 sulfonylureas. These are organic compounds containing a sulfonyl group with the structure R-S(=O)2-R', where R' is an urea.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Sulfonylureas
Direct Parent
Sulfonylureas
Alternative Parents
Sulfonohydrazides / Sulfonyls / Semicarbazides / Organic carbonic acids and derivatives / Organopnictogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds / Alkyl chlorides
Substituents
Sulfonylurea / Sulfonohydrazide / Semicarbazide / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl / Carbonic acid derivative / Organic oxygen compound / Alkyl halide / Alkyl chloride
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available

Drug created on November 18, 2007 11:28 / Updated on June 04, 2019 06:19