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Status:
US Approved Rx
(2015)
Source:
NDA206192
(2015)
Source URL:
First approved in 2015
Source:
NDA206192
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Cobimetinib is an orally active, potent and highly selective small molecule inhibiting mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), and central components of the RAS/RAF/MEK/ERK signal transduction pathway. It has been approved in Switzerland and the US, in combination with vemurafenib for the treatment of patients with unresectable or metastatic BRAF V600 mutation-positive melanoma. Preclinical studies have demonstrated that Cobimetinib is effective in inhibiting the growth of tumor cells bearing a BRAF mutation, which has been found to be associated with many tumor types. A threonine-tyrosine kinase and a key component of the RAS/RAF/MEK/ERK signalling pathway that is frequently activated in human tumors, MEK1 is required for the transmission of growth-promoting signals from numerous receptor tyrosine kinases. Cobimetinib is used in combination with vemurafenib because the clinical benefit of a BRAF inhibitor is limited by intrinsic and acquired resistance. Reactivation of the MAPK pathway is a major contributor to treatment failure in BRAF-mutant melanomas, approximately ~80% of melanoma tumors becomes BRAF-inhibitor resistant due to reactivation of MAPK signalling. BRAF-inhibitor resistant tumor cells are sensitive to MEK inhibition, therefore cobimetinib and vemurafenib will result in dual inhibition of BRAF and its downstream target, MEK. Cobimetinib specifically binds to and inhibits the catalytic activity of MEK1, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation. Cobimetinib and vemurafenib target two different kinases in the RAS/RAF/MEK/ERK pathway. Cobimetinib is used for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. Cobimetinib is used in combination with vemurafenib, a BRAF inhibitor. Cobimetinib is marketed under the trade name Cotellic.
Status:
US Approved Rx
(2018)
Source:
NDA211358
(2018)
Source URL:
First approved in 2015
Source:
NDA206038
Source URL:
Class (Stereo):
CHEMICAL (ACHIRAL)
Lumacaftor (VX-809) is an investigational drug developed by the Massachusetts-based pharmaceutical company Vertex for the treatment of patients who suffer from cystic fibrosis (CF) and have the F508del mutation in the CF transmembrane conductance regulator (CFTR). Currently, lumacaftor is approved by the U.S. FDA as a combined oral treatment for CF in combination with Kalydeco (ivacaftor). Lumacaftor is commercialized by Vertex under the brand name Orkambi, and Kalydeco was approved in the United States in 2012. The lumacaftor/Kalydeco combo was approved by the FDA in July 2015 for patients ages 12 and older, while the use of lumacaftor alone is still being studied by Vertex. The mechanism of action of lumacaftor is based on the interference with the F508 CFTR. The chronic disease is caused by a mutation in the gene that controls the salt transportation in the cells, resulting in thick, sticky mucus in the respiratory, digestive, and reproductive systems. To address that genetic defect, lumacaftor helps correct the mutated genes with a novel therapeutic approach. Both lumicaftor and kalydeco work by correcting the misfolded CFTR protein, the root cause of the F508del mutation, which led to the approval of the combined treatment by the FDA. However, while kalydeco alone is also approved by the FDA, the use of lumacftor alone has not yet been approved.
Status:
US Approved Rx
(2015)
Source:
NDA207103
(2015)
Source URL:
First approved in 2015
Source:
NDA207103
Source URL:
Class (Stereo):
CHEMICAL (ACHIRAL)
Palbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6 indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein. Inhibition of these proteins leads to reduced phosphorylation of Rb, inhibition of downstream signalling, and increased tumor growth arrest. Palbociclib received an accelerated approval from the Food and Drug Administration on February 3, 2015. Palbociclib is marketed under the trade name Ibrance. IBRANCE is a kinase inhibitor indicated in combination with letrozole for the
treatment of postmenopausal women with estrogen receptor (ER)-positive,
human epidermal growth factor receptor 2 (HER2)-negative advanced breast
cancer as initial endocrine-based therapy for their metastatic disease.
Status:
US Approved Rx
(2015)
Source:
NDA208462
(2015)
Source URL:
First approved in 2015
Source:
NDA208462
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Targets:
Ixazomib (trade name Ninlaro) is a drug for the treatment of multiple myeloma in adults after at least one prior therapy, in combination with lenalidomide and dexamethasone. It is taken by mouth in form of capsules. Common side effects include diarrhea, constipation and low platelet count. Like the older bortezomib (which can only be given by injection), it acts as a proteasome inhibitor, has orphan drug status in the US and Europe. At therapeutic concentrations, ixazomib selectively and reversibly inhibits the protein proteasome subunit beta type-5 (PSMB5) with a dissociation half-life of 18 minutes. This mechanism is the same as of bortezomib, which has a much longer dissociation half-life of 110 minutes; the related drug carfilzomib, by contrast, blocks PSMB5 irreversibly. Proteasome subunits beta type-1 and type-2 are only inhibited at high concentrations reached in cell culture models. PSMB5 is part of the 20S proteasome complex and has enzymatic activity similar to chymotrypsin. It induces apoptosis, a type of programmed cell death, in various cancer cell lines. A synergistic effect of ixazomib and lenalidomide has been found in a large number of myeloma cell lines. The medication is taken orally as a prodrug, ixazomib citrate, which is a boronic ester; this ester rapidly hydrolyzes under physiological conditions to its biologically active form, ixazomib, a boronic acid. Absolute bioavailability is 58%, and highest blood plasma concentrations of ixazomib are reached after one hour. Plasma protein binding is 99%.
Status:
US Approved Rx
(2015)
Source:
NDA204958
(2015)
Source URL:
First approved in 2015
Source:
NDA204958
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Cangrelor is a P2Y12 inhibitor that has been approved as an antiplatelet drug. It is marketed in the US under the brand name Kengreal and in Europe as Kengrexal. Cangrelor is an intravenous, direct-acting reversible P2Y12 inhibitor for patients undergoing percutaneous coronary intervention.
Status:
US Approved Rx
(2022)
Source:
NDA213092
(2022)
Source URL:
First approved in 2015
Source:
NDA206947
Source URL:
Class (Stereo):
CHEMICAL (ACHIRAL)
Targets:
Lenvatinib, developed by Eisai Co., is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. These receptor tyrosine kinases (RTKs) located in the cell membrane play a central role in the activation of signal transduction pathways involved in the normal regulation of cellular processes, such as cell proliferation, migration, apoptosis and differentiation, and in pathogenic angiogenesis, lymphogenesis, tumour growth and cancer progression. In particular, VEGF has been identified as a crucial regulator of both physiologic and pathologic angiogenesis and increased expression of VEGF is associated with a poor prognosis in many types of cancers. Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer. Most patients with thyroid cancer have a very good prognosis with treatment (98% 5 year survival rate) involving surgery and hormone therapy. However, for patients with RAI-refractory thyroid cancer, treatment options are limited and the prognosis is poor, leading to a push for the development of more targeted therapies such as lenvatinib. Lenvatinib is marketed under the trade name Lenvima, it is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.
Status:
US Approved Rx
(2015)
Source:
NDA206500
(2015)
Source URL:
First approved in 2015
Source:
NDA206500
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Rolapitant (VARUBI) is neurokinin 1 (NK1) receptor antagonist. Rolapitant does not have significant affinity for the NK2 or NK3 receptors. Drug is indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Most common adverse reactions are: neutropenia and hiccups at Cisplatin Based Highly Emetogenic Chemotherapy; decreased appetite, neutropenia and dizziness at Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide. Inhibition of BCRP and P-gp by rolapitant can increase plasma concentrations of the concomitant drug and potential for adverse reactions. Strong CYP3A4 Inducers (e.g., rifampin) can significantly reduce plasma concentrations of rolapitant and decrease the efficacy of VARUBI.
Status:
US Approved Rx
(2015)
Source:
NDA208169
(2015)
Source URL:
First approved in 2015
Source:
NDA208169
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Conditions:
Uridine triacetate is used to treat an overdose of capecitabine or fluorouracil. In addition, it is used as a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation. Uridine competitively inhibits cell damage and cell death caused by fluorouracil. Uridine can be used by essentially all cells to make uridine nucleotides, compensating for the genetic deficiency in synthesis in patients with hereditary orotic aciduria. When intracellular uridine nucleotides are restored into the normal range, overproduction of orotic acid is reduced by feedback inhibition, so that urinary excretion of orotic acid is also reduced. Adverse reactions occurring in >2% of patients receiving uridine triacetate included vomiting, nausea, and diarrhea. In vitro data showed that uridine triacetate was a weak substrate for P-glycoprotein. Due to the potential for high local (gut) concentrations of the drug after dosing, the interaction of uridine triacetate with orally administered P-gp substrate drugs cannot be ruled out.
Status:
US Approved Rx
(2014)
Source:
NDA205436
(2014)
Source URL:
First approved in 2014
Source:
NDA205436
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Tedizolid (also known as TR-700, DA-7157) as is an active compound, which is produced by plasma or intestinal phosphatases, after administration of the drug, tedizolid phosphate either orally or intravenously. The mechanism of action of tedizolid occurs through inhibition of bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit, thereby preventing the formation of the 70S initiation complex and inhibiting protein synthesis.
Status:
US Approved Rx
(2021)
Source:
ANDA211969
(2021)
Source URL:
First approved in 2014
Source:
NDA203567
Source URL:
Class (Stereo):
CHEMICAL (ABSOLUTE)
Conditions:
Efinaconazole is triazole used as a 10% topical solution for the treatment of onychomycosis, a fungal infection of the nails. It was approved for use in Canada and the USA in 2014 and is marketed by Valeant Pharmaceuticals North America LLC under the name Jublia. Like other antifungal triazoles, efinaconazole inhibits the fungal cytochrome P450 enzyme lanosterol 14α demethylase (CYP51), thereby disrupting ergosterol synthesis and, consequently, membrane integrity and growth in fungi. CYP51 is evolutionarily conserved and, in mammals, mediates conversion of lanosterol to meiosis-activating sterols (MAS); MAS are intermediates in the biosynthesis of cholesterol and may have a signaling role in initiating meiosis and oocyte maturation. Azoles have higher affinity for fungal CYP51 compared to the mammalian enzyme and such selectivity contributes to the safety of this therapeutic class. Azoles have been reported to produce reproductive and developmental toxicity in both humans and laboratory animals. The mechanism is unknown but inhibition of mammalian CYP51 as well as other CYPs, e.g. CYP17, CYP19 and CYP26, have been postulated to play a role.