pemetrexed
Trade name: alimta
Approved
Feb 4, 2004
Pemetrexed is a new-generation antifolate, approved for the treatment of mesothelioma and non-small cell lung cancer, currently being evaluated for the treatment of a variety of other solid tumors. Pemetrexed, is a folate analog metabolic inhibitor that exerts its action by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GARFT) and and to a lesser extent aminoimidazole carboxamide ribonucleotide formyltransferase (AICARFT), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, is thought to occur to a lesser extent, in normal tissues. Polyglutamated metabolites are thought to have an increased intracellular half-life resulting in prolonged drug action in malignant cells. — NCATS
Clinical trial activity
1,066 trials · 515 clinical orgs · 32 marketing orgs
Earliest trial started Sep 1, 1997 (NCT00003711)
Timeline
2000s
- Jan 1, 2000
Earliest Phase 2 Sponsor(trial)
- Aug 28, 2001
Orphan Drug Designation
- Feb 4, 2004
Earliest FDA Approval
2010s
- Jul 31, 2015
Hospira — Marketing Organization
- Oct 27, 2015
Accord Research — Marketing Organization
- Apr 18, 2016
Teva — Marketing Organization
- May 31, 2016
Abraxis — Marketing Organization
- May 19, 2017
Qilu Pharmaceutical Co., Ltd. — Marketing Organization
- Mar 28, 2018
Apotex — NDA Secondary Org
- May 4, 2018
Biocon Limited — Marketing Organization
- Dec 28, 2018
Jiangsu Hansoh Pharmaceutical Co., Ltd. — Marketing Organization
- Aug 28, 2019
Mylan — Marketing Organization
- Oct 17, 2019
Nang Kuang Pharmaceutical Co., Ltd. — Marketing Organization
2020s
- Feb 8, 2020
Eagle Pharmaceuticals, Inc. — Marketing Organization
- Feb 8, 2020
Eagle Pharmaceuticals, Inc. — NDA Secondary Org
- May 1, 2020
Fresenius — Marketing Organization
- May 14, 2020
Dr. Reddy's Laboratories — Marketing Organization
- May 14, 2020
Dr. Reddy's Laboratories — NDA Secondary Org
- Aug 21, 2020
Actavis — Marketing Organization
- Aug 21, 2020
AbbVie — NDA Secondary Org
- May 6, 2021
Sandoz — Marketing Organization
- Jun 24, 2021
Zydus Discovery DMCC — Marketing Organization
- May 25, 2022
Apotex — Marketing Organization
- May 25, 2022
Eugia Pharma — Marketing Organization
- May 25, 2022
Waverley Pharma International Inc — Marketing Organization
- May 25, 2022
Pfizer — Marketing Organization
- May 25, 2022
Reliance Life Sciences Pvt. Ltd — Marketing Organization
- May 26, 2022
Novartis — NDA Secondary Org
- Jun 10, 2022
Pfizer — NDA Secondary Org
- Jul 19, 2022
Accord Research — NDA Secondary Org
- Aug 4, 2022
Amneal Pharmaceuticals — Marketing Organization
- Aug 18, 2022
Baxalta — Marketing Organization
- Aug 18, 2022
Takeda — Marketing Organization
- Dec 13, 2022
Meitheal — Marketing Organization
- Dec 13, 2022
Eu Yan Sang — Marketing Organization
- Mar 10, 2023
PHARMOBEDIENT — Marketing Organization
- May 22, 2023
Shilpa Medicare Ltd. — Marketing Organization
- May 22, 2023
Shilpa Medicare Ltd. — NDA Secondary Org
- Dec 11, 2023
Prinston Inc — Marketing Organization
- Jun 14, 2024
Hetero Labs Ltd — Marketing Organization
Indications
Studied for
- Adenocarcinoma · Phase 4
- Adenocarcinoma, Bronchiolo-Alveolar · Phase 2
- Adenocarcinoma of Lung · Phase 4
- Angiogenesis Modulating Agents · Phase 2
- Antineoplastic Agents · Phase 1/Phase 2
- Bevacizumab · Phase 2
- Bile Duct Neoplasms · Phase 1/Phase 2
- Biliary Tract Neoplasms · Phase 2
- Biomarkers · Phase 2
- Brain Neoplasms · Phase 2
- Breast Neoplasms · Phase 2
- Breast Neoplasms, Male · Phase 2
- Bronchial Diseases · Phase 3
- Bronchial Neoplasms · Phase 3
- Carcinoma · Phase 3
- Carcinoma, Adenoid Cystic · Phase 2
- Carcinoma, Bronchogenic · Phase 3
- Carcinoma, Ductal · Phase 2
- Carcinoma, Non-Small-Cell Lung · Phase 4
- Carcinoma, Pancreatic Ductal · Phase 1
- Carcinoma, Renal Cell · Phase 2
- Carcinoma, Small Cell · Phase 2
- Carcinoma, Squamous Cell · Phase 3
- Carcinoma, Transitional Cell · Phase 3
- Central Nervous System Neoplasms · Phase 2
- Cervical Intraepithelial Neoplasia · Phase 2
- Chemotherapy, Adjuvant · Phase 2
- Chordoma · Phase 2
- Choriocarcinoma · Phase 2
- Circulating Tumor DNA · Phase 2
- Colorectal Neoplasms · Phase 2
- Cytoreduction Surgical Procedures · Phase 2
- Diabetes Mellitus, Type 2 · Phase 1
- Docetaxel · Phase 2
- Drug-Related Side Effects and Adverse Reactions · Phase 3
- Drugs, Investigational · Phase 4
- Drug Therapy · Phase 2
- Drug Therapy, Combination · Phase 1/Phase 2
- Endometrial Neoplasms · Phase 2
- Ependymoma · Phase 2
- Epidermal Growth Factor · Phase 3
- Erb-b2 Receptor Tyrosine Kinases · Phase 3
- ErbB Receptors · Phase 2
- Esophageal Neoplasms · Phase 2
- Fallopian Tube Neoplasms · Phase 2
- Gallbladder Neoplasms · Phase 1/Phase 2
- Gastrointestinal Neoplasms · Phase 2
- General Surgery · Phase 2
- Genes, erbB-1 · Phase 2
- Genes, erbB-2 · Phase 2
- Genes, ras · Phase 1/Phase 2
- Genital Neoplasms, Female · Phase 2
- Gestational Trophoblastic Disease · Phase 2
- Glioma · Phase 2
- Granulocyte-Macrophage Colony-Stimulating Factor · Phase 2
- Hamartoma · Phase 2
- Head and Neck Neoplasms · Phase 3
- Healthy Volunteers · Phase 1
- Hydatidiform Mole · Phase 2
- Immune Checkpoint Inhibitors · Phase 2
- Immunotherapy · Phase 2
- Lapatinib · Phase 1/Phase 2
- Leukemia · Early Phase 1
- Liver Neoplasms · Phase 2
- Lung Diseases · Phase 3
- Lung Neoplasms · Phase 3
- Lymphoma · Phase 3
- Lymphoma, Large-Cell, Immunoblastic · Phase 2
- Lymphoma, Non-Hodgkin · Phase 1
- Lymphoproliferative Disorders · Early Phase 1
- Medical Oncology · Phase 1
- Medulloblastoma · Phase 2
- Melanoma · Phase 2
- Mesothelioma · Phase 4
- Mesothelioma, Malignant · Phase 3
- Multiple Myeloma · Early Phase 1
- Mutation · Phase 3
- Myelodysplastic Syndromes · Early Phase 1
- Myeloproliferative Disorders · Early Phase 1
- Nasopharyngeal Neoplasms · Phase 2
- Neoadjuvant Therapy · Phase 2
- Neoplasm Metastasis · Phase 4
- Neoplasms · Phase 4
- Neoplasms by Histologic Type · Phase 3
- Neoplasms by Site · Phase 3
- Neoplasms, Germ Cell and Embryonal · Phase 3
- Neoplasms, Nerve Tissue · Phase 3
- Neuregulin-1 · Phase 2
- Neuroblastoma · Phase 2
- Neuroendocrine Tumors · Phase 2
- Oncogene Proteins · Phase 2
- Oncogenes · Phase 2
- Osteosarcoma · Phase 2
- Ovarian Neoplasms · Phase 3
- Pancreatic Neoplasms · Phase 3
- Pemetrexed · Phase 2
- Peritoneal Neoplasms · Phase 2
- Pharmacokinetics · Phase 1
- Pharmacological and Toxicological Phenomena · Phase 2
- Pleura · Phase 2
- Pleural Neoplasms · Phase 2
- Positron Emission Tomography Computed Tomography · Phase 2
- Precancerous Conditions · Early Phase 1
- Primary Myelofibrosis · Early Phase 1
- Progression-Free Survival · Phase 2
- Prostatic Neoplasms · Phase 2
- Protein Kinase Inhibitors · Phase 1/Phase 2
- Proto-Oncogene Proteins c-met · Phase 2
- Radiation Oncology · Phase 2
- Radiosurgery · Phase 2
- Radiotherapy · Phase 3
- ras GTPase-Activating Proteins · Phase 1
- ras Proteins · Phase 1
- Rectal Neoplasms · Phase 2
- Respiratory Tract Diseases · Phase 3
- Respiratory Tract Neoplasms · Phase 3
- Rhabdomyosarcoma · Phase 2
- Safety · Phase 2
- Salivary Gland Neoplasms · Phase 2
- Sarcoma · Phase 2
- Sarcoma, Ewing · Phase 2
- Small Cell Lung Carcinoma · Phase 3
- Squamous Cell Carcinoma of Head and Neck · Phase 2
- Stomach Neoplasms · Phase 3
- Therapeutics · Phase 2
- Thoracic Neoplasms · Phase 3
- Thymidylate Synthase · Phase 2
- Thymoma · Phase 2
- Thymus Neoplasms · Phase 1
- Thyroid Neoplasms · Phase 2
- Triple Negative Breast Neoplasms · Phase 2
- Trophoblastic Neoplasms · Phase 2
- Ureteral Neoplasms · Phase 3
- Urethral Neoplasms · Phase 2
- Urinary Bladder Neoplasms · Phase 3
- Urogenital Neoplasms · Phase 2
- Urologic Neoplasms · Phase 2
- Uterine Cervical Neoplasms · Phase 3
- Uterine Neoplasms · Phase 2
Mechanism of action
- Dihydrofolate reductaseINHIBITOR
DHFR inhibitor
- GAR transformylaseINHIBITOR
GART inhibitor
- Thymidylate synthaseINHIBITOR
TYMS inhibitor
Approval history
- approvedPriority reviewFast trackFeb 4, 2004
Chemistry & pharmacology
SMILES
Nc1nc2[nH]cc(CCc3ccc(C(=O)N[C@@H](CCC(=O)[O-])C(=O)[O-])cc3)c2c(=O)[nH]1.[Na+].[Na+]- Mol. weight
- 471.38 g/mol
- Lipinski Ro5
- 1 violation(s)
- Rule of 3
- No
- Chirality
- Single Stereoisomer
- Inorganic
- No
- Polymer
- No
- Delivery
- Parenteral
- Availability
- Prescription Only
Oral
No
Parenteral
Yes
Topical
No
Sources
- ChEMBLCHEMBL2360464 ↗
- WikipediaPemetrexed ↗
- NCATS04Q9AIZ7NO ↗
- ChEMBLCHEMBL225072 ↗
- ChEMBLCHEMBL1201258 ↗
- ChEMBLCHEMBL1200373 ↗
Also known as
- alimta
- alimta
- alimta
- alimta
- alimta
- pemebit
- pemetrexed
- pemetrexed
- pemetrexed
- pemetrexed
- pemetrexed
- pemetrexed
- pemetrexed
- pemetrexed
- pemetrexed
- pemetrexed
- pemetrexed diacid monohydrate
- pemetrexed diacid monohydrate
- pemetrexed diacid monohydrate
- pemetrexed diacid monohydrate
- pemetrexed diacid monohydrate
- pemetrexed diacid monohydrate
- pemetrexed diacid monohydrate
- pemetrexed disodium
- pemetrexed disodium
- pemetrexed disodium
- pemetrexed disodium
- pemetrexed disodium
- pemetrexed disodium hemipentahydrate
- pemetrexed disodium heptahydrate
- pemetrexed ditromethamine
- pemetrexed sodium
- pemetrexed sodium
- pemetrexed sodium hydrate
- trc102
- trc 102
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07279935 | Phase 4 | Jan 15, 2026 | AstraZeneca |
| NCT07252739 | Phase 2 | Jan 14, 2026 | Merck |
| NCT06999980 | Phase 2 | Dec 31, 2025 | Bristol-Myers Squibb, Melanoma Institute Australia |
| NCT07309952 | Phase 2 | Dec 31, 2025 | Sun Yat-Sen University |
| NCT06522360 | Phase 2 | Dec 1, 2025 | University of Texas at Houston |
| NCT07229339 | Phase 2 | Dec 1, 2025 | Otsuka, University of California, Los Angeles |
| NCT07020065 | Phase 2 | Nov 30, 2025 | Swiss Cancer Institute |
| NCT07256509 | Phase 2 | Nov 30, 2025 | Shijiazhuang Pharma Group (CSPC) |
| NCT07128199 | Phase 3 | Nov 30, 2025 | Otsuka |
| NCT07063745 | Phase 2/Phase 3 (Phase 3) | Nov 28, 2025 | Bristol-Myers Squibb |
| NCT07100080 | Phase 2/Phase 3 (Phase 3) | Nov 5, 2025 | Bristol-Myers Squibb |
| NCT07131319 | Phase 2/Phase 3 (Phase 3) | Oct 30, 2025 | Nanchang University |
| NCT06996782 | Phase 1/Phase 2 (Phase 2) | Oct 13, 2025 | AstraZeneca |
| NCT07190248 | Phase 3 | Oct 8, 2025 | Merck |
| NCT06899126 | Phase 3 | Oct 7, 2025 | Daiichi Sankyo, Merck |
| NCT07181499 | Phase 2 | Sep 30, 2025 | Betta Pharmaceuticals Co.,Ltd., Jiangmen Central Hospital, Sun Yat-Sen University, The First People's Hospital of Zhaoqing City, Xiamen University |
| NCT07171606 | Phase 2 | Sep 30, 2025 | Sunshine Lake Pharma Co., Ltd. |
| NCT07174908 | Phase 3 | Sep 30, 2025 | Chinese Academy of Medical Sciences, InxMed (Shanghai) Co., Ltd., Jiao Tong University |
| NCT07178795 | Phase 3 | Sep 29, 2025 | Baili Pharmaceutical Group |
| NCT07154368 | Phase 3 | Sep 23, 2025 | Government of China |
Organizations
Research & Development (515)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Eli Lilly | For profit | 171 | 118 | 5 | 1998 |
| National Cancer Institute (NCI) | Government | 104 | 40 | 4 | 1998 |
| Merck | For profit | 59 | 35 | 3 | 2005 |
| AstraZeneca | For profit | 48 | 33 | 4 | 2005 |
| Roche | For profit | 33 | 25 | 4 | 2006 |
| Sun Yat-Sen University | Academic/Hospital | 33 | 24 | 3 | 2007 |
| Bristol-Myers Squibb | For profit | 31 | 19 | 3 | 2005 |
| Genentech | For profit | 25 | 6 | 3 | 2005 |
| Chinese Academy of Medical Sciences | Academic/Hospital | 24 | 16 | 5 | 2010 |
| Jiao Tong University | Academic/Hospital | 24 | 14 | 4 | 2013 |
| University of Texas at Houston | Academic/Hospital | 20 | 17 | 2 | 1997 |
| Huazhong University of Science and Technology | Academic/Hospital | 17 | 11 | 3 | 2013 |
| Fudan University | Academic/Hospital | 15 | 13 | 4 | 2009 |
| Guangzhou Medical University | Academic/Hospital | 15 | 13 | 2 | 2009 |
| Novartis | For profit | 14 | 9 | 3 | 2006 |
| Hengrui Therapeutics, Inc. | For profit | 13 | 10 | 2 | 2016 |
| Tianjin Medical University | Academic/Hospital | 13 | 11 | 3 | 2019 |
| Mayo Clinic | Academic/Hospital | 12 | 4 | 2 | 2000 |
| Pfizer | For profit | 12 | 11 | 3 | 2005 |
| Boehringer Ingelheim | For profit | 11 | 9 | 3 | 2005 |
Marketing (48)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| AbbVie | For profit | NDA2 | Aug 21, 2020 |
| Abraxis | For profit | MKTG | May 31, 2016 |
| Accord Research | For profit | MKTG | May 25, 2022 |
| Accord Research | For profit | MKTG | Oct 27, 2015 |
| Accord Research | For profit | NDA2 | Jul 19, 2022 |
| Actavis | For profit | MKTG | Aug 21, 2020 |
| Actavis | For profit | SYN | Aug 21, 2020 |
| Amneal Pharmaceuticals | For profit | MKTG | Aug 4, 2022 |
| Apotex | For profit | MKTG | May 25, 2022 |
| Apotex | For profit | NDA2 | Mar 28, 2018 |
| Baxalta | For profit | MKTG | Aug 18, 2022 |
| Biocon Limited | For profit | SYN | May 23, 2019 |
| Biocon Limited | For profit | MKTG | May 25, 2022 |
| Biocon Limited | For profit | MKTG | May 4, 2018 |
| Dr. Reddy's Laboratories | For profit | MKTG | May 25, 2022 |
| Dr. Reddy's Laboratories | For profit | MKTG | May 14, 2020 |
| Dr. Reddy's Laboratories | For profit | NDA2 | May 14, 2020 |
| Eagle Pharmaceuticals, Inc. | For profit | MKTG | Feb 8, 2020 |
| Eagle Pharmaceuticals, Inc. | For profit | NDA2 | Feb 8, 2020 |
| Eli Lilly | For profit | NDA | — |
| Eli Lilly | For profit | SYN | Feb 4, 2004 |
| Eu Yan Sang | For profit | MKTG | Dec 13, 2022 |
| Eugia Pharma | For profit | MKTG | May 25, 2022 |
| Fresenius | For profit | MKTG | May 1, 2020 |
| Hetero Labs Ltd | For profit | MKTG | Jun 14, 2024 |
| Hospira | For profit | MKTG | May 25, 2022 |
| Hospira | For profit | MKTG | Jul 31, 2015 |
| Jiangsu Hansoh Pharmaceutical Co., Ltd. | For profit | MKTG | Dec 28, 2018 |
| Meitheal | For profit | MKTG | Dec 13, 2022 |
| Mylan | For profit | MKTG | Aug 28, 2019 |
| Nang Kuang Pharmaceutical Co., Ltd. | For profit | MKTG | Oct 17, 2019 |
| Novartis | For profit | NDA2 | May 26, 2022 |
| PHARMOBEDIENT | For profit | MKTG | Mar 10, 2023 |
| Pfizer | For profit | NDA2 | Jun 10, 2022 |
| Pfizer | For profit | MKTG | May 25, 2022 |
| Prinston Inc | For profit | MKTG | Dec 11, 2023 |
| Qilu Pharmaceutical Co., Ltd. | For profit | MKTG | May 25, 2022 |
| Qilu Pharmaceutical Co., Ltd. | For profit | MKTG | May 19, 2017 |
| Reliance Life Sciences Pvt. Ltd | For profit | MKTG | May 25, 2022 |
| Sandoz | For profit | SYN | May 26, 2022 |
| Sandoz | For profit | MKTG | May 6, 2021 |
| Shilpa Medicare Ltd. | For profit | MKTG | May 22, 2023 |
| Shilpa Medicare Ltd. | For profit | NDA2 | May 22, 2023 |
| Takeda | For profit | MKTG | Aug 18, 2022 |
| Teva | For profit | MKTG | Apr 18, 2016 |
| Waverley Pharma International Inc | For profit | MKTG | May 25, 2022 |
| Zydus Discovery DMCC | For profit | MKTG | May 25, 2022 |
| Zydus Discovery DMCC | For profit | MKTG | Jun 24, 2021 |