Table 4. The pharmacological details of the drugs currently in use or being developed for MCL. Please see Supplementary Table 4 to access complete table.

FRONTLINE DRUGS
	Generic name Trade/Pipeline Name(s)	Company/FDA Approval year	Chemical structure	Drug Class	Status/Route	Target/Mechanism of action	Toxicity	References
1	Chlorambucil Leukeran Ambochlorin Amboclorin Linfozilin	ASPEN GLOBAL INC, 1957		Alkylating agent	Prescription/Oral	Target: DNA synthesis. Mechanism of action: Binds DNA preventing –DNA synthesis. –RNA transcription. –Mutagenic effect. Induces cellular apoptosis: –Accumulation of cytosolic p53. –Activation of Bax.	Hematologic: Bone marrow suppression, anemia, leukopenia, neutropenia, thrombocytopenia, pancytopenia. Gastrointestinal: Gastrointestinal disturbances Dermatologic: urticaria, angioneurotic edema, skin hypersensitivity. Other: pulmonary fibrosis, hepatotoxicity, fever, peripheral neuropathy, interstitial pneumonia, sterile cystitis, infertility, leukemia, secondary malignancies.	[277]
2	Lenalidomide Revlimid	CELGENE, 2005		Immunomodulatory Agent	Prescription/Oral	Target: TNF-alpha inhibitor. Mechanism of action: Increases tumor cell apoptosis: –Enhancing IL-10 Induces G0-G1 cell cycle arrest: –CDK2 inhibition. T- cells activated via B7 pathway: –Tyrosine phosphorylation of CD28.	Hematologic: Neutropenia, thrombocytopenia, anemia. Other: pneumonia, fatigue.	[278]
3	Ibrutinib Imbruvica	PHARMACYCLICS INC, 2014		Antineoplastic Agent/Bruton tyrosine kinase inhibitor	Prescription/Oral	Target: Bruton's tyrosine kinase inhibitor Mechanism of action: Inhibits BTK and activates pathways necessary for B-cell trafficking, chemotaxis, and adhesion. Promotes cancer cell apoptosis, inhibits cell proliferation.	Gastrointestinal: Diarrhea, nausea, peripheral edema, constipation, vomiting, loss of appetite. Other: fatigue, dyspnea, upper respiratory tract infection.	[279]
4	Methotrexate TrexallRasuvoOtrexupMexate	BARR, 2001MEDAC PHARMA INC, 2014ANTARES PHARMA INC, 2013BRISTOL, 1979		Antineoplastic Agent, Antipsoriatic, Antirheumatic, Cytotoxic	Prescription/Injection, Sub-cuteneous	Target: Dihydrofolate reductase inhibitor Mechanism of action: Inhibits folic acid reductase, hinders DNA synthesis and prevents cellular replication.	Hematologic: aplastic anemia, pancytopenia, leukopenia, neutropenia. Other: lymphadenopathy, drowsiness, blurred vision, cognitive dysfunction, moodiness, tinnitus, mucositis.	[280]
5	Fludarabine FludaraOforta	GENZYME CORP, 1991SANOFI AVENTIS US, 2008		Purine Nucleotides, Antimetabolites Antineoplastic Agents	Prescription/Intravenous, Oral	Target: DNA synthesis inhibitor Mechanism of action: Inhibition of ribonucleotide reductase, incorporation into DNA: repression of DNA polymerization Inhibition of DNA ligase and DNA primase.	Hematologic: neutropenia, thrombocytopenia, anemia, lymphocytopenia. Gastrointestinal: nausea, vomiting. Other: infection (typically respiratory tract), fever, elevation of liver enzymes.	[281]
6	Ibritumomab tiuxetan Zevalin	SPECTRUM PHARMS, 2002		Carboxylic Acids and Derivatives	Prescription/Intravenous	Target: CD20 Mechanism of action: Ibritumomab tiuxetan binds to the CD20 antigen on Bcells. The CD20 antigen is not shed from the cell surface and does not internalize upon antibody binding. The chelate tiuxetan binds Y-90, is covalently linked to ibritumomab. The beta emission from Y-90 induces cellular damage: formation of free radicals in the targeted and neighboring cells.	Hematologic: Haemopoetic, myelosuppression	[282]
7	Temsirolimus Torisel	PF PRISM CV, 2007		mTOR inhibitor, Antineoplastic agent	Prescription/Intravenous	Target: mammalian target of rapamycin (mTOR) inhibitor Mechanism of action: Binds to FKBP-12, and the protein-drug complex inhibits mTOR. Inhibition of mTOR activity results in a G1 growth arrest in treated tumor cells.	Hematologic: thrombocytopenia, asthenia, anemia. Gastrointestinal: diarrhea. Other: fever.	[283]
8	Cyclo-phosphamide CytoxanNeosar	BAXTER HLTHCARE, 1959TEVA PARENTERAL, 1993BEDFORD, 1982		Alkylating agents	Prescription/Oral, intravenous	Target: DNA Mechanism of action: Forms DNA crosslinks both between and within DNA strands at guanine N-7 positions leading to cell apoptosis.	Dermatologic: alopecia. Other: haemorrhagic cystitis, immunosuppression (when not desired).	[284]
9	Vincristine Marqibo Kit Oncovin Vincrex Vincasar PFS Leurocristine	TALON THERAP, 2012LILLY, 1963BRISTOL MYERS SQUIBB, 1988TEVA PARENTERAL, 1987		Antineoplastic Agents, Phytogenic	Prescription/Intravenous	Target: beta-tubulin, tubulin polymerization inhibitor Mechanism of action: Inhibits cell division during early mitosis. Binds to tubulin monomers preventing the formation of spindle microtubules. Stops the separation of the duplicated chromosomes and prevents cell division.	Other: acute uric acid nephropathy, acute shortness of breath and severe bronchospasm.	[285]
10	Doxorubicin Adriamycin PFS Rubex Doxil	PHARMACIA AND UPJOHN, 1987BRISTOL MYERS SQUIBB, 1989JANSSEN RES AND DEV, 1995		Antibiotics, Antineoplastic, Anthracyclines.	Prescription/Intravevous	Target: topoisomerase II inhibitor Mechanism of action: Doxorubicin is oxidized to an unstable metabolite and converted back to doxorubicin in a process that releases reactive oxygen species, this leads to lipid peroxidation and membrane damage, DNA damage, oxidative stress, and triggers apoptotic pathways of cell death. Alternatively, doxorubicin can enter the nucleus and poison topoisomerase-II, also resulting in DNA damage and cell death.	Other: acute and chronic cardiotoxicity/cardiomyopathy.	[286]
11	Dexamethasone Ciprodex Decaderm Decadron Dexamethasone Hexadrol Maxidex Ozurdex Tobradex ST	ALCON PHARMS LTD, 2003 MERCK, N/AMERCK, 1958 ECR, 2008 SANDOZ, 1971 WATSON LABS, 1973 PVT FORM, 1973 PHOENIX LABS NY, 1974 MUTUAL PHARM, 1974 ROXANE, 1975 STI PHARMA LLC, 1976 PAR PHARM, 1983 LYNE, 2011 VINTAGE PHARMS, 2011 ORGANON USA INC, 1962 ALCON, 1962 ALLERGAN, 2009 ALCON PHARMS LTD, 2009		Glucocorticoid, Corticosteroid	Prescription/intravenous, intramuscular, intra-articular, intralesional and soft tissue injection	Target: glucocorticoid receptor agonist Mechanism of action: Inhibition of inflammatory agents in the body, implicated in the development or growth of some cancers.	Gastrointestinal: gastritis. Other: cushingoid facies, obesity, glucose intolerance, hypertension, psychologic alterations, infections, myositis and myopathy, avascular necrosis of bone.	[287]
12	Cytarabine Cytosar-UDepocyt	TEVA PARENTERAL, 1969 EUROHLTH INTL SARL, 1989 HOSPIRA, 1990 FRESENIUS KABI USA, 2004 MYLAN LABS LTD, 2011 TEVA PHARMS USA, 1998 PACIRA PHARMS INC, 1999		Antimetabolite antineoplastic agent, Nucleoside Metabolic Inhibitor	Prescription/Intravenous, Intrathecal, or Subcutaneous	Target: DNA polymerase inhibitor Mechanism of action: Damages the S phase of cell cycle. Inhibits both DNA and RNA polymerases and nucleotide reductase enzymes needed for DNA synthesis.	Hematologic: anemia, leukopenia, thrombocytopenia, megaloblastosis. Other: infection, Ara-C syndrome.	[288]
RELAPSED DRUGS
13	Bendamustine Treanda Ribomustin Levact Cytostasan SDX-105	CEPHALON, 2008		Alkylating/Antineoplastic Agent	Prescription/intravenous injection	Target: DNA Mechanism of action: Activation of DNA damage stress response and apoptosis induced by p21 (Cip1/Waf1) and Noxa, inhibition of mitotic checkpoints, and induction of mitotic catastrophe	Hematologic: febrile neutropenia. Other: fatigue, pneumonia, hypokalemia dehydration, pyrexia.	[289]