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Disease ID:1194
Associated with:1 target
1 immuno-relevant target
4 immuno-relevant ligands
A disease caused by mast cell hyperplasia.
Database Links
Disease Ontology: DOID:350


KIT proto-oncogene, receptor tyrosine kinase
Comments:  Constitutively active KIT D816V is associated with mast cell clonal disorders. KIT D816V detection in blood and bone marrow is important for diagnosing systemic mastocytosis.
References:  8,11
Mutations:  KIT proto-oncogene, receptor tyrosine kinase is associated with 1 mutation. Click here for details
Ligand interactions: 
Ligand Comments
EMA orphan drug for mastocytosis.


Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
brentuximab vedotin
Immuno Disease Comments: Phase 2 clinical candidate for aggressive systemic mastocytosis, mast cell leukemia and systemic mastocytosis- see NCT01807598
Clinical Use: Brentuximab vedotin is an anti-neoplastic agent used in the treatment of Hodgkin's lymphoma [9] and systemic anaplastic large cell lymphoma. Several clinical trials are evaluating the combination of brentuximab vedotin with immune checkpoint inhibitors, to assess any synergistic effects as a result of dual targeting. Checkpoint inhibitors being investigated in this way include and (both anti-PD-1), and (anti-CTLA4). Brentuximab vedotin + pembrolizumab (NCT02684292) and brentuximab vedotin + nivolumab (NCT03138499) are both Phase 3 studies in patients with relapsed/refractory classical Hodgkin's lymphoma.

Expanded approvals:
In November 2017, the FDA approved brentuximab vedotin for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, following review of results from the Phase 3 ALCANZA trial (NCT01578499) [4]. In March 2018, the FDA approved the use of brentuximab vedotin for the treatment of patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy. This expansion was based on results from the ECHELON-1 clinical trial (NCT01712490) [2,14]. November 2018 saw further expansion of approval for the use of brentuximab vedotin plus chemotherapy for adult patients who are newly diagnosed with CD30-expressing peripheral T-cell lymphomas. | View clinical data
Bioactivity Comments: Detailed information contained in the covering patent [5] describes in vitro and in vivo activity of the invention, which supports its anti-CD30 action. However, no affinity data is provided for the interaction between the antibody and its molecular target. | View biological activity
Immuno Disease Comments: FDA approved drug for aggressive systemic mastocytosis and systemic mastocytosis with associated hematological neoplasm or mast cell leukemia. EMA orphan drug for mastocytosis.
Clinical Use: The FDA granted midostaurin accelerated approval in April 2017, and the EMA followed in September of the same year. These authorisations are for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive (as detected by an FDA-approved test) to be used in combination with standard and induction and cytarabine consolidation. It was also approved for mastocytosis [6]. The EMA had previously granted midostaurin orphan drug designation for the treatment of AML and mastocytosis (effective via inhibition of KIT receptors on mast cells, which are involved in stimulating proliferation of mast cells in mastocytosis).
Click here to link to's list of Phase 2 midostaurin trials. | View clinical data
Bioactivity Comments: Midostaurin inhibits proliferation of cells carrying FLT3 translocations or single amino acid changes, and inhibits autophosphorylation of mutant FLT3 receptors [13]. | View biological activity
Immuno Disease Comments: EMA orphan drug for mastocytosis.
Clinical Use: The European Medicines Agency has granted masitinib orphan designation as a treatment for pancreatic cancer, amyotrophic lateral sclerosis (ALS, a.k.a. motor neurone disease, MND) and mastocytosis. It has been evaluated in clinical trials for a number of inflammatory conditions, solid tumours, multiple myeloma, ALS and Alzheimer's disease. Click here to link to's complete listing of masitinib trials (note that many of these are not active or have been terminated). In June 2021, a Phase 3 study testing the safety and effectiveness of masitinib as an add-on treatment to for ALS was announced by AB Science. | View clinical data
Bioactivity Comments: This compound is primarily an inhibitor of type III receptor tyrosine kinases, but has some inhibitory activity at non-receptor tyrosine kinases [3]. | View biological activity
cromoglicic acid
Immuno Disease Comments: Mast cell stabiliser used to treat mastocytosis.
Clinical Use: Cromoglicic acid is available in different formulations; nasal spray is used to treat allergic rhinitis, nebulizer solution to treat asthma, eye drops to treat allergic conjunctivitis and an oral form to treat mastocytosis, dermatographic urticaria and ulcerative colitis. Clinical use in asthma has largely been replaced by the more convenient leukotriene receptor antagonists. | View clinical data
Bioactivity Comments: As the precise MMOA of this drug has not been fully resolved, we have not tagged a primary drug target in this case. | View biological activity


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1. Bibi S, Zhang Y, Hugonin C, Mangean MD, He L, Wedeh G, Launay JM, Van Rijn S, Würdinger T, Louache F et al.. (2016) A new humanized in vivo model of KIT D816V+ advanced systemic mastocytosis monitored using a secreted luciferase. Oncotarget, 7 (50): 82985-83000. [PMID:27783996]

2. Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, Picardi M et al.. (2018) Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med, 378 (4): 331-344. [PMID:29224502]

3. Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Castéran N, Borge L, Hajem B, Lermet A, Sippl W et al.. (2009) Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS ONE, 4 (9): e7258. [PMID:19789626]

4. FDA. FDA approves Brentuximab vedotin for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma. Accessed on 10/11/2017. Modified on 10/11/2017.,

5. Francisco JA, Risdon G, Wahl AF, Siegall C. (2006) immunotherapy; fusion proteins; antitumor agents; for treatment and prevention of hodgkin's disease. Patent number: US7090843. Assignee: Seattle Genetics, Inc. Priority date: 09/12/2014. Publication date: 15/08/2006.

6. Gallogly MM, Lazarus HM, Cooper BW. (2017) Midostaurin: a novel therapeutic agent for patients with FLT3-mutated acute myeloid leukemia and systemic mastocytosis. Ther Adv Hematol, 8 (9): 245-261. [PMID:29051803]

7. Greiner G, Gurbisz M, Ratzinger F, Witzeneder N, Simonitsch-Klupp I, Mitterbauer-Hohendanner G, Mayerhofer M, Müllauer L, Sperr WR, Valent P et al.. (2018) Digital PCR: A Sensitive and Precise Method forKITD816V Quantification in Mastocytosis. Clin Chem, 64 (3): 547-555. [PMID:29237714]

8. Kristensen T, Vestergaard H, Bindslev-Jensen C, Mortz CG, Kjaer HF, Ollert M, Møller MB, Broesby-Olsen S, Mastocytosis Centre Odense University Hospital (MastOUH). (2017) Prospective evaluation of the diagnostic value of sensitive KIT D816V mutation analysis of blood in adults with suspected systemic mastocytosis. Allergy, 72 (11): 1737-1743. [PMID:28432683]

9. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A et al.. (2015) Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 385 (9980): 1853-62. [PMID:25796459]

10. Onnes MC, Tanno LK, Elberink JN. (2016) Mast Cell Clonal Disorders: Classification, Diagnosis and Management. Curr Treat Options Allergy, 3 (4): 453-464. [PMID:27942432]

11. Pardanani A. (2019) Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management. Am J Hematol, 94 (3): 363-377. [PMID:30536695]

12. Taylor ML, Sehgal D, Raffeld M, Obiakor H, Akin C, Mage RG, Metcalfe DD. (2004) Demonstration that mast cells, T cells, and B cells bearing the activating kit mutation D816V occur in clusters within the marrow of patients with mastocytosis. J Mol Diagn, 6 (4): 335-42. [PMID:15507672]

13. Weisberg E, Boulton C, Kelly LM, Manley P, Fabbro D, Meyer T, Gilliland DG, Griffin JD. (2002) Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell, 1 (5): 433-43. [PMID:12124173]

14. Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. (2013) Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol, 14 (13): 1348-56. [PMID:24239220]