NAV

Laromustine

Identification

Generic Name
Laromustine
DrugBank Accession Number
DB05817
Background

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.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 307.775
Monoisotopic: 307.00633966
Chemical Formula
C6H14ClN3O5S2
Synonyms
  • Cloretazine
  • Laromustine
  • Onrigin
External IDs
  • 101M
  • VNP 40101M
  • VNP-40101M
  • VNP40101M
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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.

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Contraindications & Blackbox Warnings
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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

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Products

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International/Other Brands
Cloretazine

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aliphatic acyclic compound / Alkyl chloride / Alkyl halide / Carbonic acid derivative / Carbonyl group / Hydrocarbon derivative / Organic oxide / Organic oxygen compound / Organic sulfonic acid or derivatives / Organochloride
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
14J2G0U3NQ
CAS number
173424-77-6
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
1-[N-(2-chloroethyl)methanesulfonamido]-1-methanesulfonyl-3-methylurea
SMILES
CNC(=O)N(N(CCCl)S(C)(=O)=O)S(C)(=O)=O

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. [Article]
PubChem Compound
3081349
PubChem Substance
175427039
ChemSpider
2338969
ChEMBL
CHEMBL167691
ZINC
ZINC000001544545

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentLeukemias1
2CompletedTreatmentLeukemias / Myelodysplastic Syndrome / Myeloproliferative/Myelodysplastic Neoplasm1
2CompletedTreatmentLung Cancer1
2Unknown StatusTreatmentLeukemias1
1CompletedTreatmentBrain and Central Nervous System Tumors1

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)13.27Chemaxon
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-MSsplash10-0059-9320000000-b91d532a7cfd0864eefa
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-77f54be1981b8caaf191
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0901000000-a0919a01254d57b051ea
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-9701000000-ee72b17e3e83b13604a9
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9430000000-53772451f689f124fde0
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-05gs-9400000000-48c4deb583dfd03e58f9
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9000000000-d0ef5b966a5cb3a734c9
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-157.18753
predicted
DeepCCS 1.0 (2019)
[M+H]+159.54553
predicted
DeepCCS 1.0 (2019)
[M+Na]+165.63869
predicted
DeepCCS 1.0 (2019)

Drug created at November 18, 2007 18:28 / Updated at January 14, 2023 19:03