strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs act nonspecifically. Agents requiring activation Some of the substances require conversion into active substances in vivo (e.g., cyclophosphamide). Cyclophosphamide is one of the most potent immunosuppressive substances. In small dosages, it is very efficient in the therapy of systemic lupus erythematosus, autoimmune hemolytic anemia, granulomatosis with polyangiitis, and other autoimmune diseases. High dosages cause pancytopenia and hemorrhagic cystitis. Dialkylating agents, limpet attachment, and monoalkylating agents Dialkylating agents can react with two different 7-N-guanine residues, and, if these are in different strands of DNA, the result is cross-linkage of the DNA strands, which prevents uncoiling of the DNA double helix. If the two guanine residues are in the same strand, the result is called limpet attachment of the drug molecule to the DNA. Busulfan is an example of a dialkylating agent: it is the methanesulfonate diester of 1,4-butanediol. Methanesulfonate can be eliminated as a leaving group. Both ends of the molecule can be attacked by DNA bases, producing a butylene crosslink between two different bases. Monoalkylating agents can react only with one 7-N of guanine. Limpet attachment and monoalkylation do not prevent the separation of the two DNA strands of the double helix but do prevent vital DNA-processing enzymes from accessing the DNA. The final result is inhibition of cell growth or stimulation of apoptosis, cell suicide. Examples In the Anatomical Therapeutic Chemical Classification System, alkylating agents are classified under L01A. Classical alkylating agents Many of the agents are known as "classical alkylating agents". These include true alkyl groups, and have been known for a longer time than some of the other alkylating agents. Examples include melphalan and chlorambucil. The following three groups are almost always considered "classical". Nitrogen mustards Cyclophosphamide — the most widely used alkylating agent of modern times. Chlormethine also known as mechlorethamine or mustine (HN2) — the first alkylating agent to receive regulatory approval. Uramustine or uracil mustard Melphalan Chlorambucil Ifosfamide Bendamustine Nitrosoureas Carmustine Lomustine Streptozocin Alkyl sulfonates Busulfan Alkylating-like Platinum-based chemotherapeutic drugs (termed platinum analogues) act in a similar manner. These agents do not have an alkyl group, but nevertheless damage DNA. They permanently coordinate to DNA to interfere with DNA repair, so they are sometimes described as "alkylating-like". Platinum Cisplatin Carboplatin Dicycloplatin Eptaplatin Lobaplatin Miriplatin Nedaplatin Oxaliplatin Picoplatin Satraplatin Triplatin tetranitrate These agents also