DNA Alkylator/Crosslinker

Cisplatin (CDDP) is a DNA cross-linking agent. Cisplatin has antitumor activity and inhibits DNA synthesis by forming DNA adducts in cancer cells. Cisplatin also activates iron death and induces autophagy.

Oxaliplatin (L-OHP) is a DNA alkylating agent, an inhibitor of DNA synthesis. Oxaliplatin causes DNA cross-linking damage, preventing DNA replication and transcription and leading to cell death. Oxaliplatin induces autophagy.

Temozolomide (TMZ) is a DNA alkylating agent with blood-brain barrier permeability and oral activity. Temozolomide has antitumor activity and antiangiogenic activity, and also induces apoptosis and autophagy. Temozolomide is stable under acidic conditions and hydrolyzes under neutral or slightly alkaline conditions.

Streptozocin (NSC-85998) is an antibiotic that induces DNA methylation. Streptozocin is toxic to insulin-producing pancreatic islet B-cells and is commonly used in the construction of animal models of type 1 diabetes. The product is unstable in solution and is recommended to be dispensed now.

N-Nitroso-N-methylurea is a nitrosourea compound with alkylating, carcinogenic and mutagenic properties. It targets a variety of animal organs, causes various cancers and degenerative diseases, and can be used in diazomethane synthesis.

Illudin M is a cytotoxic sesquiterpene from the fungus O. illudens that alkylates DNA. It has a cytotoxicity of 6-100 nM against HL-60 human leukemia cells.Illudin M has anticancer activity and is a pre-drug for the synthesis of anticancer compounds.

Semustine, a DNA alkylating agent, is a cancer chemotherapy compound that is nephrotoxic in patients with malignant melanoma receiving adjuvant chemotherapy for the adjuvant treatment of leukemia.

Carmustine (bis-chloroethylnitrosourea) is a cell-cycle phase nonspecific alkylating antineoplastic agent.

Carboplatin (JM-8) is a cisplatin derivative, a DNA synthesis inhibitor. Carboplatin binds to DNA, inhibits replication and transcription, and induces cell death. Carboplatin has antitumor activity.

Bendamustine hydrochloride (EP-3101) (IC50 of 50 μM) is an alkylating agent associated with DNA damage.

Cyclophosphamide hydrate is a DNA alkylating agent, an inhibitor of DNA synthesis. Cyclophosphamide hydrate has antitumor and immunosuppressive activities.

Illudin S (ILS) is a fungal sesquiterpene secondary metabolite with potent genotoxic and cytotoxic properties.

VAL-083 is an alkylating agent with antitumor activity that produces N7 methylation on DNA.

Miriplatin (SM-11355) (SM-11355) is a platinum complex used in TACE that has promise for the therapy of hepatocellular carcinoma (HCC).

RITA (NSC-652287)(NSC-652287) induced cross-links of both DNA-DNA and DNA-protein with no detectable DNA single-strand breaks. RITA, like nutlin-3, can disrupt the p53/Mdm2 interaction.

PK11000 is a p53 targeting compound, has anti-tumor activities through activation of unstable p53.

Pipobroman (Vercyte) is an anti-cancer drug that probably acts as an alkylating agent. Pipobroman has well documented clinical activity in polycythemia vera (PV) and essential thrombocythemia (ET). Pipobroman allows, within 3 months, to attain a response in more than 90% of patients, without clinically relevant toxicities. The 10-years risk of thrombosis of patients treated with Pipobroman is about 15%, The anti-proliferative activity of Pipobroman on bone marrow megakaryocytes seems of particular value in lowering the occurrence of post-PV and post-ET MMM, whose risk is the lowest registered with available treatments. The 10-year risk of acute leukemia with Pipobroman is 5% in PVand 3% in ET, which is only slightly higher than that expected as a natural evolution of the disease. In conclusion, the use of Pipobroman is a definite alternative to hydroxyurea in patients with PV and ET at high risk of thrombosis.

Ifosfamide (NSC-109724) alkylates and forms DNA crosslinks, thereby preventing DNA strand separation and DNA replication. Ifosfamide is a synthetic analog of the nitrogen mustard cyclophosphamide with antineoplastic activity. This agent is a prodrug that must be activated through hydroxylation by hepatic microsomal enzymes.

Trioxsalen (Trioxysalen) is a furanocoumarin and a psoralen derivative, in conjunction with UV-A for phototherapy treatment of vitiligo and hand eczema. After photoactivation it creates interstrand cross-links in DNA, which can cause programmed cell death.

CB1954(Tretazicar (NSC-115829)), an anticancer prodrug, is activated by NAD(P)H quinone oxidoreductase 2. It is converted in the presence of the enzyme NQO2 and co-substrate caricotamide ( EP-0152R) (EP) into a potent cytotoxic bifunctional alkylating agent.

Altretamine (ENT-50852) is an alkylating agent with antineoplastic activity.

KCC-07 is a selective, potent and brain-penetrant inhibitor of methyl-CpG-binding domain protein 2(MBD2) with anticancer activity. KCC-07 prevents binding of MBD2 to methylated DNA and activates brain specific angiogenesis inhibitor 1 (BAI1) inducing anti

Busulfan (Busulphan) is a synthetic derivative of dimethane-sulfonate with antineoplastic and cytotoxic properties. Although its mechanism of action is not fully understood, busulfan appears to act through the alkylation of DNA. Following systemic absorption of busulfan, carbonium ions are formed, resulting in DNA alkylation and DNA breaks and inhibition of DNA replication and RNA transcription.

Cyclophosphamide is an alkylating agent used in the treatment of several forms of cancer including leukemias, lymphomas and breast cancer.

Satraplatin (BMS182751) is an orally available antineoplastic platinum(IV) complex.Satraplatin has a favorable toxicity profile and appears to have clinical activity against a variety of malignancies.

Thio-TEPA (Tiofosyl) is a polyfunctional, organophosphorus alkylating agent with antineoplastic activity.

Chlorambucil (CB-1348) is an orally-active antineoplastic aromatic nitrogen mustard. Chlorambucil alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis.

Lomustine (NSC-79037) is an alkylating agent of value against both hematologic malignancies and solid tumors.

Procarbazine hydrochloride (NSC-77213 HCl) is the hydrochloride salt of a methylhydrazine derivative with antineoplastic and mutagenic activities. Although the exact mode of cytotoxicity has not been elucidated, procarbazine, after metabolic activation, appears to inhibit the trans-methylation of methionine into transfer RNA (t-RNA), thereby preventing protein synthesis and consequently DNA and RNA synthesis. This agent may also undergo auto-oxidation, resulting in the formation of cytotoxic free radicals which damage DNA through an alkylation reaction.

Nimustine Hydrochloride (Nidran hydrochloride) has been used in trials studying the treatment of Glioblastoma.

Bendamustine (SDX105) for the treatment of Non-Hodgkin Lymphomas and Chronic Lymphocytic Leukemia

Palifosfamide (Isophosphamide mustard) lysine (ZIO-201) is a stable form of palifosfamide. Palifosfamide lysine has broad activity in sarcoma lines in vitro. The IC50 ranges from 2.25 to 6.75 μM for most cell lines except OS222 (IC50=31.5 μM).

Treosulfan (Treosulphan) is a bifunctional alkylating agent. It also has activity in ovarian cancer and other solid tumor types.