GILTERITINIB FUMARATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C29H44N8O3.C4H4O4
Molecular Weight	1221.4951
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.CCC1=C(NC2CCOCC2)N=C(NC3=CC=C(N4CCC(CC4)N5CCN(C)CC5)C(OC)=C3)C(=N1)C(N)=O.CCC6=C(NC7CCOCC7)N=C(NC8=CC=C(N9CCC(CC9)N%10CCN(C)CC%10)C(OC)=C8)C(=N6)C(N)=O

InChI

InChIKey=UJOUWHLYTQFUCU-WXXKFALUSA-N

InChI=1S/2C29H44N8O3.C4H4O4/c2*1-4-23-28(31-20-9-17-40-18-10-20)34-29(26(33-23)27(30)38)32-21-5-6-24(25(19-21)39-3)37-11-7-22(8-12-37)36-15-13-35(2)14-16-36;5-3(6)1-2-4(7)8/h2*5-6,19-20,22H,4,7-18H2,1-3H3,(H2,30,38)(H2,31,32,34);1-2H,(H,5,6)(H,7,8)/b;;2-1+

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf
Curator's Comment: Description was created based on several sources, including https://ash.confex.com/ash/2016/webprogram/Paper92543.html | http://www.activebiochem.com/Product/Gilteritinib.html | https://www.ncbi.nlm.nih.gov/pubmed/26279055 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf

Gilteritinib, also known as ASP2215, is a potent FLT3/AXL inhibitor, which showed potent antileukemic activity against AML with either or both FLT3-ITD and FLT3-D835 mutations. In in vitro, among the 78 tyrosine kinases tested, Gilteritinib inhibited FLT3, LTK, ALK, and AXL kinases by over 50% at 1 nM with an IC50 value of 0.29 nM for FLT3, approximately 800-fold more potent than for c-KIT, the inhibition of which is linked to a potential risk of myelosuppression. Gilteritinib inhibited the growth of MV4-11 cells, which harbor FLT3-ITD, with an IC50 value of 0.92 nM, accompanied with inhibition of pFLT3, pAKT, pSTAT5, pERK, and pS6. Gilteritinib decreased tumor burden in bone marrow and prolonged the survival of mice intravenously transplanted with MV4-11 cells. In previous preclinical studies, gilteritinib has demonstrated superior antitumor effects when given in combination with AraC and either DNR or IDR compared with combination chemotherapy. In November 2018, the FDA approved gilteritinib for treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Tyrosine-protein kinase receptor UFO 14 Target ID: CHEMBL4895 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26555154	Inhibitor 8297	1.0 nM [IC50]
ALK tyrosine kinase receptor 25 Target ID: CHEMBL4247 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	Inhibitor 8297
Tyrosine-protein kinase receptor FLT3 43 Target ID: CHEMBL1974 Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=752319	Inhibitor 8297	0.29 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute myeloid leukemia 136 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	Primary		Approved 8429	XOSPATA Approved Use XOSPATA is a kinase inhibitor indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. Launch Date 2018

C_max

Value	Dose	Analyte	Population
137 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1257 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
216 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
216.38 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30039554	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1528 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
374 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
374 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GILTERITINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
107.6 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	40 mg 1 times / day steady, oral dose: 40 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
136.7 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	120 mg single, oral dose: 120 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
1462 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	200 mg 1 times / day steady, oral dose: 200 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
1525 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
1528 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	450 mg 1 times / day steady, oral dose: 450 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
168.2 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	200 mg single, oral dose: 200 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
204.3 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
207.6 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	450 mg single, oral dose: 450 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
24.9799999999999 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	40 mg single, oral dose: 40 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
374.2 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	120 mg 1 times / day steady, oral dose: 120 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
376.4 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	80 mg 1 times / day steady, oral dose: 80 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
75.29 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	80 mg single, oral dose: 80 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:

AUC

Value	Dose	Analyte	Population
2446 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28711 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3324 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3340.23 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30039554	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
37468 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6943 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6943 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GILTERITINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1216 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	80 mg single, oral dose: 80 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
2480 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	120 mg single, oral dose: 120 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
2482 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	40 mg 1 times / day steady, oral dose: 40 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
3022 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	200 mg single, oral dose: 200 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
31005 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
31428 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	200 mg 1 times / day steady, oral dose: 200 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
3324 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	450 mg single, oral dose: 450 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
34768 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	450 mg 1 times / day steady, oral dose: 450 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
360 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	40 mg single, oral dose: 40 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
4163 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
6943 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	120 mg 1 times / day steady, oral dose: 120 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
6958 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	80 mg 1 times / day steady, oral dose: 80 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
1216 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	80 mg single, oral dose: 80 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
1990 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	40 mg 1 times / day steady, oral dose: 40 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
2480 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	120 mg single, oral dose: 120 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
2544 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	450 mg single, oral dose: 450 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
3024 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	200 mg single, oral dose: 200 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
31749 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
32248 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	200 mg 1 times / day steady, oral dose: 200 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
35506 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	450 mg 1 times / day steady, oral dose: 450 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
360.4 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	40 mg single, oral dose: 40 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
4181 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
6943 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	120 mg 1 times / day steady, oral dose: 120 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
7111 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	80 mg 1 times / day steady, oral dose: 80 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:

T_1/2

Value	Dose	Analyte	Population
159 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
84 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30039554	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
113 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
113 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GILTERITINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
45.8499999999999 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	120 mg 1 times / day steady, oral dose: 120 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
141.9 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	200 mg 1 times / day steady, oral dose: 200 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
142.2 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	300 mg 1 times / day steady, oral dose: 300 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
151.8 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	40 mg 1 times / day steady, oral dose: 40 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
86.11 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02014558	80 mg 1 times / day steady, oral dose: 80 mg route of administration: oral experiment type: steady co-administered:	GILTERITINIB plasma	Homo sapiens population: unhealthy age: sex: food status:

F_unbound

Value	Dose	Analyte	Population
6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32304015	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GILTERITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	120 mg 1 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GILTERITINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211349s001lbl.pdf		GILTERITINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 1 times / day multiple, oral MTD Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/32304015	unhealthy, 62 years (range: 21–90 years) n = 252 Health Status: unhealthy Condition: relapsed AML \| refractory FLT3 mutation-positive AML Age Group: 62 years (range: 21–90 years) Sex: M+F Population Size: 252 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/32304015	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/32304015
300 mg single, oral MTD Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/32304015	unhealthy, 62 years (range: 21–90 years) n = 252 Health Status: unhealthy Condition: relapsed AML \| refractory FLT3 mutation-positive AML Age Group: 62 years (range: 21–90 years) Sex: M+F Population Size: 252 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/32304015	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf https://pubmed.ncbi.nlm.nih.gov/32304015
450 mg 1 times / day multiple, oral Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32304015	unhealthy, 62 years (range: 21–90 years) n = 252 Health Status: unhealthy Condition: relapsed AML \| refractory FLT3 mutation-positive AML Age Group: 62 years (range: 21–90 years) Sex: M+F Population Size: 252 Sources: https://pubmed.ncbi.nlm.nih.gov/32304015	Sources: https://pubmed.ncbi.nlm.nih.gov/32304015
450 mg single, oral Dose: 450 mg Route: oral Route: single Dose: 450 mg Sources: https://pubmed.ncbi.nlm.nih.gov/32304015	unhealthy, 62 years (range: 21–90 years) n = 252 Health Status: unhealthy Condition: relapsed AML \| refractory FLT3 mutation-positive AML Age Group: 62 years (range: 21–90 years) Sex: M+F Population Size: 252 Sources: https://pubmed.ncbi.nlm.nih.gov/32304015	Sources: https://pubmed.ncbi.nlm.nih.gov/32304015
120 mg 1 times / day steady, oral Recommended Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	unhealthy n = 292 Health Status: unhealthy Condition: relapsed AML \| refractory AML Population Size: 292 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	Disc. AE: Pneumonia, Sepsis... AEs leading to discontinuation/dose reduction: Pneumonia (2%) Sepsis (2%) Dyspnea (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf

AEs

AE	Significance	Dose	Population
Dyspnea	1% Disc. AE	120 mg 1 times / day steady, oral Recommended Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	unhealthy n = 292 Health Status: unhealthy Condition: relapsed AML \| refractory AML Population Size: 292 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf
Pneumonia	2% Disc. AE	120 mg 1 times / day steady, oral Recommended Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	unhealthy n = 292 Health Status: unhealthy Condition: relapsed AML \| refractory AML Population Size: 292 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf
Sepsis	2% Disc. AE	120 mg 1 times / day steady, oral Recommended Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf	unhealthy n = 292 Health Status: unhealthy Condition: relapsed AML \| refractory AML Population Size: 292 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MATE1 306 BCRP 699 OCT2 647 CYP3A 214 CYP2C19 1478 OATP1B1 788 MATE2 263	P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	strong [IC50 1.4 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	strong [IC50 2.9 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	weak [IC50 29 uM]
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	weak [IC50 48 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	weak [IC50 62 uM]
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	weak [IC50 63 uM]	weak (co-administration study) Comment: gilteritinib increased cmax of midazolam by 10% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	yes [IC50 0.054 uM]	no (co-administration study) Comment: gilteritinib decreased cmax of cephalexin by 3-9% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf	yes		yes (co-administration study) Comment: itraconazole increased exposure of gilteritinib by 2.2x Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/211349Orig1s000MultidisciplineR.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:145372	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:145372
ChemicalBook	CB82725626	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB82725626
MolPort	MolPort-038-934-933	https://www.molport.com/shop/molecule-link/MolPort-038-934-933
ZINC	ZINC000113476229	http://zinc15.docking.org/substances/ZINC000113476229

PubMed

Title	Date	PubMed
Preliminary data on ASP2215: tolerability and efficacy in acute myeloid leukemia patients.	2015 Sep	26279055
FLT3 Inhibitors for Treating Acute Myeloid Leukemia.	2016 Oct	27450971
Inhibition of FLT3 in AML: a focus on sorafenib.	2017 Mar	27775694

Patents

Sample Use Guides

In Vivo Use Guide

120 mg orally once-daily

Route of Administration: Oral

In Vitro Use Guide

Gilteritinib inhibited the growth of MV4-11 cells, which harbor FLT3-ITD, with an IC50 value of 0.92 nM

Name

Type

Language

GILTERITINIB FUMARATE

Official Name

English

Gilteritinib fumarate [WHO-DD]

Common Name

English

GILTERITINIB HEMIFUMARATE

Common Name

English

GILTERITINIB FUMARATE [USAN]

Common Name

English

XOSPATA

Brand Name

English

2-PYRAZINECARBOXAMIDE, 6-ETHYL-3-((3-METHOXY-4-(4-(4-METHYL-1-PIPERAZINYL)-1-PIPERIDINYL)PHENYL)AMINO)-5-((TETRAHYDRO-2H-PYRAN-4-YL)AMINO)-, (2E)-2-BUTENEDIOATE (2:1)

Systematic Name

English

ASP2215 HEMIFUMARATE

Code

English

GILTERITINIB FUMARATE [JAN]

Common Name

English

ASP-2215 HEMIFUMARATE

Code

English

GILTERITINIB FUMARATE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1967