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
- Weight
- Average: 307.775
Monoisotopic: 307.00633966 - Chemical Formula
- C6H14ClN3O5S2
- Synonyms
- Cloretazine
- Laromustine
- Onrigin
- External IDs
- 101M
- VNP 40101M
- VNP-40101M
- VNP40101M
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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- 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- 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
- 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]
- External Links
- PubChem Compound
- 3081349
- PubChem Substance
- 175427039
- ChemSpider
- 2338969
- ChEMBL
- CHEMBL167691
- ZINC
- ZINC000001544545
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Leukemias 1 2 Completed Treatment Leukemias / Myelodysplastic Syndrome / Myeloproliferative/Myelodysplastic Neoplasm 1 2 Completed Treatment Lung Cancer 1 2 Unknown Status Treatment Leukemias 1 1 Completed Treatment Brain and Central Nervous System Tumors 1
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
Property Value Source Water Solubility 0.736 mg/mL ALOGPS logP -0.01 ALOGPS logP -1.9 Chemaxon logS -2.6 ALOGPS pKa (Strongest Acidic) 13.27 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 103.86 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 61.91 m3·mol-1 Chemaxon Polarizability 26.65 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8559 Blood Brain Barrier + 0.8044 Caco-2 permeable - 0.6019 P-glycoprotein substrate Non-substrate 0.6696 P-glycoprotein inhibitor I Non-inhibitor 0.8511 P-glycoprotein inhibitor II Non-inhibitor 0.9551 Renal organic cation transporter Non-inhibitor 0.8851 CYP450 2C9 substrate Non-substrate 0.5 CYP450 2D6 substrate Non-substrate 0.6957 CYP450 3A4 substrate Non-substrate 0.5549 CYP450 1A2 substrate Non-inhibitor 0.8237 CYP450 2C9 inhibitor Non-inhibitor 0.6915 CYP450 2D6 inhibitor Non-inhibitor 0.8751 CYP450 2C19 inhibitor Non-inhibitor 0.6605 CYP450 3A4 inhibitor Non-inhibitor 0.9463 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9028 Ames test AMES toxic 0.6094 Carcinogenicity Non-carcinogens 0.5844 Biodegradation Not ready biodegradable 0.7946 Rat acute toxicity 3.0136 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7836 hERG inhibition (predictor II) Non-inhibitor 0.9204
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0059-9320000000-b91d532a7cfd0864eefa Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0009000000-77f54be1981b8caaf191 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0901000000-a0919a01254d57b051ea Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-9701000000-ee72b17e3e83b13604a9 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-9430000000-53772451f689f124fde0 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05gs-9400000000-48c4deb583dfd03e58f9 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-9000000000-d0ef5b966a5cb3a734c9 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 157.18753 predictedDeepCCS 1.0 (2019) [M+H]+ 159.54553 predictedDeepCCS 1.0 (2019) [M+Na]+ 165.63869 predictedDeepCCS 1.0 (2019)
Drug created at November 18, 2007 18:28 / Updated at January 14, 2023 19:03