Filters
Custom request?
Type
Production region
Qualifications
Country of origin
Dabrafenib API Manufacturers & Suppliers
2 verified results
All Dabrafenib data. Full access. Full negotiation power
Commercial-scale Suppliers
Employees: 50+
All certificates
All certificates
Total market transparency
Supplier trade data access
Buyer / supplier flow comparison
Dabrafenib | CAS No: 1195765-45-7 | GMP-certified suppliers
A medication that treats BRAF-mutated unresectable or metastatic melanoma, non-small cell lung cancer, anaplastic thyroid cancer, and select pediatric solid tumors by targeting tumor growth.
Therapeutic categories
Primary indications
- As monotherapy, dabrafenib is indicated to treat unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test
- In combination with [trametinib], dabrafenib is indicated to treat for:
- The treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test
Product Snapshot
- Dabrafenib is formulated as an oral small molecule in capsule and tablet forms, including coated and suspension tablets
- It is primarily indicated for the treatment of unresectable or metastatic melanoma, non-small cell lung cancer, anaplastic thyroid cancer, and certain solid tumors harboring BRAF V600E or V600K mutations, often used in combination with trametinib
- Dabrafenib holds approved status in the US, Canada, and the EU, with indications supported by FDA-approved companion diagnostic tests
Clinical Overview
Clinically, dabrafenib is indicated as monotherapy for unresectable or metastatic melanoma harboring the BRAF V600E mutation confirmed by an FDA-approved diagnostic test. In combination with trametinib, a MEK inhibitor, dabrafenib is approved for treating unresectable or metastatic melanoma with BRAF V600E or V600K mutations, including adjuvant melanoma therapy post-resection with lymph node involvement. This combination is also indicated for metastatic NSCLC with BRAF V600E mutation, locally advanced or metastatic ATC with the same mutation where no satisfactory local treatments exist, and for select pediatric solid tumors and low-grade glioma with BRAF V600E mutations. Notably, dabrafenib is not indicated for colorectal cancer or tumors with wild-type BRAF due to intrinsic resistance.
Pharmacodynamically, dabrafenib inhibits mutated BRAF kinase by competitively binding its ATP-binding pocket, thereby disrupting downstream MAPK signaling and reducing tumor proliferation. Combination therapy with trametinib targets sequential kinases within the pathway, improving efficacy and reducing resistance mechanisms without additive toxicity. Clinical efficacy data supporting melanoma indications derive from pivotal Phase III trials such as COMBI-AD.
From an ADME perspective, dabrafenib undergoes extensive hepatic metabolism primarily via cytochrome P450 enzymes. It is both a substrate and modulator of various CYP isoforms, including CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4, necessitating careful consideration of drug-drug interactions. Dabrafenib also interacts with multiple drug transporters including P-glycoprotein and organic anion transporting polypeptides.
Safety considerations include the risk of cutaneous squamous cell carcinoma, fever, hyperglycemia, and potential QT prolongation. Photosensitivity reactions may occur, and monitoring is recommended during therapy. The compound is classified as a photosensitizing and potential QTc-prolonging agent.
Dabrafenib (trade name Tafinlar) has global regulatory approvals and is predominantly used within oncology settings targeting BRAF-mutated tumors. The API belongs to the chemical class of sulfanilides characterized by an aromatic sulfanilide moiety.
For sourcing and quality assurance, procurement of dabrafenib API requires adherence to stringent regulatory standards including Good Manufacturing Practices (GMP). Due to its complex synthetic pathway and sensitivity to impurities, robust analytical characterization and validation of identity, purity, and potency are critical. Stability profiles, polymorphic forms, and batch-to-batch consistency must be thoroughly controlled to ensure clinical safety and efficacy in final formulations.
Identification & chemistry
| Generic name | Dabrafenib |
|---|---|
| Molecule type | Small molecule |
| CAS | 1195765-45-7 |
| UNII | QGP4HA4G1B |
| DrugBank ID | DB08912 |
Pharmacology
| Summary | Dabrafenib is a selective ATP-competitive inhibitor targeting mutant forms of the serine/threonine-protein kinase BRAF, particularly BRAF V600E, which drives aberrant activation of the MAPK signaling pathway involved in cell proliferation and survival. By inhibiting mutant BRAF, dabrafenib disrupts downstream signaling through the RAS/RAF/MEK/ERK cascade, leading to reduced tumor cell growth and induction of apoptosis. It is primarily utilized in oncology to treat cancers harboring BRAF V600 mutations, often in combination with MEK inhibitors to enhance efficacy and overcome resistance. |
|---|---|
| Mechanism of action | Dabrafenib is a competitive and selective BRAF inhibitor by binding to its ATP pocket.[L41955, A248955] Although dabrafenib can inhibit wild-type BRAF, it has a higher affinity for mutant forms of BRAF, including BRAF V600E, BRAF V600K, and BRAF V600D. BRAF is a serine/threonine protein kinase and is involved in activating the RAS/RAF/MEK/ERK or MAPK pathway, a pathway that is implicated in cell cycle progression, cell proliferation, and arresting apoptosis.[A248960, A248965, A193614, A70135]Therefore, constitutive active mutation of BRAF such as BRAF V600E is frequently observed in many types of cancer, including melanoma, lung cancer, and colon cancer. |
| Pharmacodynamics | Dabrafenib is a kinase inhibitor that is mainly used to target BRAF V600E mutation in multiple types of cancer. Although dabrafenib and [trametinib] both inhibit the RAS/RAF/MEK/ERK pathway, they inhibit different effectors of the pathway, thus increasing response rate and mitigating resistance without cumulative toxicity. The melanoma approval for use with [trametinib] is based on results from COMBI-AD, a Phase III study of 870 patients with Stage III BRAF V600E/K mutation-positive melanoma treated with dabrafenib + trametinib after complete surgical resection. Patients received doses of dabrafenib (150 mg BID) + trametinib (2 mg QD) combination (n = 438) or matching placebos (n = 432). After a median follow-up of 2.8 years, the primary endpoint of relapse-free survival (RFS) was met. In the case of thyroid cancer, Dabrafenib plus Trametinib is the first regimen demonstrated to have potent clinical activity in BRAF V600E–mutated anaplastic thyroid cancer and is well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Serine/threonine-protein kinase B-raf | Humans | inhibitor |
| RAF proto-oncogene serine/threonine-protein kinase | Humans | inhibitor |
| Serine/threonine-protein kinase SIK1 | Humans | inhibitor |
ADME / PK
| Absorption | After oral administration, the median time to achieve peak plasma concentration (Tmax) is 2 hours. Mean absolute bioavailability of oral dabrafenib is 95%. Following a single dose, dabrafenib exposure (Cmax and AUC) increased in a dose-proportional manner across the dose range of 12 mg to 300 mg, but the increase was less than dose-proportional after repeat twice-daily dosing. After repeated twice-daily dosing of 150 mg, the mean accumulation ratio was 0.73, and the inter-subject variability (CV%) of AUC at steady-state was 38%. |
|---|---|
| Half-life | The mean terminal half-life of dabrafenib is 8 hours after oral administration. Hydroxy-dabrafenib's terminal half-life (10 hours) parallels that of dabrafenib while the carboxy- and desmethyl-dabrafenib metabolites exhibit longer half-lives (21 to 22 hours). |
| Protein binding | Dabrafenib is 99.7% bound to human plasma proteins. |
| Metabolism | The metabolism of dabrafenib is primarily mediated by CYP2C8 and CYP3A4 to form hydroxy-dabrafenib. Hydroxy-dabrafenib is further oxidized via CYP3A4 to form carboxy-dabrafenib and subsequently excreted in bile and urine. Carboxy-dabrafenib is decarboxylated to form desmethyl-dabrafenib; desmethyl-dabrafenib may be reabsorbed from the gut. Desmethyl-dabrafenib is further metabolized by CYP3A4 to oxidative metabolites. |
| Route of elimination | Fecal excretion is the major route of elimination accounting for 71% of radioactive dose while urinary excretion accounted for 23% of total radioactivity as metabolites only. |
| Volume of distribution | The apparent volume of distribution (Vc/F) is 70.3 L.Distribution to the brain is restricted because dabrafenib is a substrate and undergoes efflux by P-glycoprotein and breast cancer resistance protein. |
| Clearance | The clearance of dabrafenib is 17.0 L/h after single dosing and 34.4 L/h after 2 weeks of twice-daily dosing. |
Formulation & handling
- Dabrafenib is a small molecule oral API with limited water solubility, formulated primarily as capsules and tablets for suspension.
- It exhibits significant food interaction effects, requiring administration on an empty stomach and avoidance of grapefruit products and CYP3A4 modulators.
- Formulation considerations include low aqueous solubility and high LogP, indicating potential challenges in dissolution and absorption optimization.
Regulatory status
| Lifecycle | The API is currently patented in the United States with key patents expiring between late 2025 and mid-2031. It is marketed in the US, Canada, and the EU, indicating a phase of established market presence with several years before primary patent expirations. |
|---|
| Markets | US, Canada, EU |
|---|
Supply Chain
| Supply chain summary | Dabrafenib is manufactured and supplied by a limited number of originator companies, with branded products available primarily in the US, Canada, and EU markets. Patent expirations range from late 2025 to 2031, indicating the potential for existing or upcoming generic competition over the next several years. This patent timeline influences global supply strategies and access considerations within these key regions. |
|---|
Safety
| Toxicity | Carcinogenicity studies with dabrafenib have not been conducted. Dabrafenib increased the risk of cutaneous squamous cell carcinomas in patients in clinical trials. Dabrafenib was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay and was not clastogenic in an in vivo rat bone marrow micronucleus test. In a combined female fertility and embryo-fetal development study in rats, a reduction in fertility was noted at doses greater than or equal to 20 mg/kg/day (equivalent to the human exposure at the recommended dose based on AUC). A reduction in the number of ovarian corpora lutea was noted in pregnant females at 300 mg/kg/day (which is approximately three times the human exposure at the recommended dose based on AUC). Male fertility studies with dabrafenib have not been conducted; however, in repeat-dose studies, testicular degeneration/depletion was seen in rats and dogs at doses equivalent to and three times the human exposure at the recommended dose based on AUC, respectively. |
|---|
- Dabrafenib has not been evaluated for carcinogenicity
- Clinical data indicate an increased incidence of cutaneous squamous cell carcinomas
- No mutagenic or clastogenic effects were observed in standard in vitro and in vivo genotoxicity assays
Dabrafenib is a type of Protein kinase inhibitors
Protein kinase inhibitors are a vital subcategory of pharmaceutical active pharmaceutical ingredients (APIs) that play a crucial role in targeted cancer therapies. These inhibitors specifically target and block the activity of protein kinases, enzymes that regulate various cellular processes, including cell growth, division, and signal transduction.
Protein kinase inhibitors function by binding to the active site of protein kinases, preventing them from phosphorylating specific proteins and disrupting intracellular signaling pathways. This targeted approach inhibits the uncontrolled growth and proliferation of cancer cells, ultimately leading to their death.
The development of protein kinase inhibitors has revolutionized cancer treatment by providing more effective and less toxic alternatives to traditional chemotherapy. These drugs have demonstrated impressive results in the treatment of various cancers, including lung, breast, and leukemia.
The pharmaceutical industry invests heavily in research and development to discover novel protein kinase inhibitors with improved potency, selectivity, and pharmacokinetic properties. High-throughput screening, computational modeling, and structure-activity relationship studies are employed to identify potential lead compounds.
The success of protein kinase inhibitors in treating cancer has spurred significant interest in this subcategory of APIs. Ongoing research aims to expand their applications to other diseases, such as autoimmune disorders and neurological conditions.
In conclusion, protein kinase inhibitors are a valuable class of pharmaceutical APIs with immense potential for targeted cancer therapies. Continued advancements in this field hold promise for improved treatment outcomes and enhanced patient care.
Dabrafenib (Protein kinase inhibitors), classified under Anticancer drugs
Anticancer drugs belong to the pharmaceutical API (Active Pharmaceutical Ingredient) category designed specifically to combat cancer cells. These powerful medications play a crucial role in cancer treatment and are developed to target and destroy cancerous cells, preventing their growth and spread.
Anticancer drugs are classified based on their mode of action and can include various types such as chemotherapy drugs, targeted therapy drugs, immunotherapy drugs, and hormonal therapy drugs. Chemotherapy drugs work by interfering with the cell division process, thereby inhibiting the growth of cancer cells. Targeted therapy drugs, on the other hand, are designed to attack specific molecules or genes involved in cancer growth, minimizing damage to healthy cells. Immunotherapy drugs stimulate the body's immune system to recognize and destroy cancer cells. Hormonal therapy drugs are used in cancers that are hormone-dependent, such as breast or prostate cancer, to block the hormones that fuel cancer cell growth.
These APIs are typically synthesized through complex chemical processes in state-of-the-art manufacturing facilities. Stringent quality control measures ensure the purity, potency, and safety of these drugs. Anticancer APIs undergo rigorous testing and adhere to stringent regulatory guidelines before being approved for clinical use.
Due to their critical role in cancer treatment, anticancer drugs are in high demand worldwide. Researchers and pharmaceutical companies continually strive to develop new and more effective APIs in this category to enhance treatment outcomes and minimize side effects. The ongoing advancements in the field of anticancer drug development offer hope for improved cancer therapies and better patient outcomes.
Dabrafenib API manufacturers & distributors
Compare qualified Dabrafenib API suppliers worldwide. We currently have 2 companies offering Dabrafenib API, with manufacturing taking place in 2 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| MSN Labs. | Producer | India | India | CoA, USDMF | 119 products |
| Sinoway industrial Co.,Lt... | Distributor | China | China | CoA | 764 products |
When sending a request, specify which Dabrafenib API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
Use the list above to find high-quality Dabrafenib API suppliers. For example, you can select GMP, FDA or ISO certified suppliers. Visit our help page to learn more about sourcing APIs via Pharmaoffer.
