Dasatinib monohydrate, also known as BMS-354825 monohydrate, is an orally active, ATP-competitive dual Src/Bcr-Abl inhibitor with potent antitumor properties. It has Ki values of 16 pM for Src and 30 pM for Bcr-Abl. The IC50 values for inhibiting Bcr-Abl and Src are less than 1.0 nM and 0.5 nM, respectively. Dasatinib monohydrate exhibits significant activity against a range of targets including Bcr-Abl, Src, Lck, Yes, c-Kit, PDGFRβ, p38, Her1, Her2, FGFR-1, and MEK, with IC50 values of less than 1.0, 0.50, 0.40, 0.50, 5.0, 28, 100, 180, 720, 880, and 1700 nM, respectively. It shows antiproliferative effects on K562 chronic myelogenous leukemia (CML), PC3 human prostate cancer, MDA-MB-231 human breast cancer, and WiDr human colon cancer cell lines, with IC50 values of less than 1.0 nM, 9.4 nM, 12 nM, and 52 nM, respectively. Dasatinib monohydrate also induces apoptosis and autophagy in cells[1].
Dasatinib monohydrate/达沙替尼（一水合物） 细胞实验
Cell Line
Concentration
Treated Time
Description
References
NALM6 cells
100, 150, 200, 250, 300 nM
48 h
The combination of dexamethasone and dasatinib showed highly synergistic effects in NALM6 cells, resulting in increased apoptosis.
Nat Commun. 2023 May 22;14(1):2935.
REH GCR cells
100, 150, 200, 250, 300 nM
48 h
The combination of dexamethasone and dasatinib showed additive effects in REH GCR cells, resulting in increased apoptosis.
Nat Commun. 2023 May 22;14(1):2935.
NK92 cells
100nM
48 and 72 h
Dasatinib significantly suppressed the expression of NKG2A to one-third or even one-quarter
Front Immunol. 2019 Jan 17;9:3152.
NK92 cells
100nM
48 h
Dasatinib significantly diminished NKG2A protein expression and reduced phosphorylated p38 MAPK expression
Front Immunol. 2019 Jan 17;9:3152.
SKM-1 cells
50 nM
24 h
Dasatinib at concentrations above 50 nM prevented cytokine release and switched off-target cell killing, which were subsequently restored on removal of dasatinib.
J Immunother Cancer. 2021 Jul;9(7):e002582.
PBMCs
100 nM
24 h
Dasatinib at 100 nM significantly inhibited HLA-A2 WT1-TCB-induced SKM-1 cell killing as well as T cell proliferation and activation.
J Immunother Cancer. 2021 Jul;9(7):e002582.
Human bone marrow-derived mesenchymal stem cells (BM-MSCs)
1 μM
21 days
Dasatinib inhibited the viability and adipogenesis commitment of human BM-MSCs, reducing adipocyte differentiation.
Cardiovasc Diabetol. 2023 Aug 17;22(1):214.
DAOY cells
1, 5, 10, 50, 100 nM
1–24 h
Dasatinib significantly inhibited the proliferation of DAOY cells and induced apoptosis and autophagy.
Cancer Lett. 2014 Nov 1;354(1):68-76.
D556 cells
1, 5, 10, 50, 100 nM
1–24 h
Dasatinib significantly inhibited the proliferation of D556 cells and induced apoptosis and autophagy.
Cancer Lett. 2014 Nov 1;354(1):68-76.
PS125 cells
3, 10 nM
Combined treatment with Dasatinib and AT9283 significantly inhibited the proliferation of PS125 cells.
Cancer Lett. 2014 Nov 1;354(1):68-76.
K562 leukemia cells
10nM
Combined inhibition of JAK2 with SAR302503 and BCR-ABL1 with dasatinib significantly inhibited their self-renewal potential
Cell Stem Cell. 2016 Aug 4;19(2):177-191.
p190 cells
5 nM
48 h
To evaluate the effect of Dasatinib on the growth of p190 cells, results showed that Dasatinib fully suppressed cell growth.
Nat Med. 2010 Feb;16(2):205-13.
SUP-B15 cells
5 nM
48 h
To evaluate the effect of Dasatinib on the growth of SUP-B15 cells, results showed that Dasatinib fully suppressed cell growth.
Nat Med. 2010 Feb;16(2):205-13.
K562 cells
5 nM
48 h
To evaluate the effect of Dasatinib on the growth of K562 cells, results showed that Dasatinib fully suppressed cell growth.
Nat Med. 2010 Feb;16(2):205-13.
Dasatinib monohydrate/达沙替尼（一水合物） 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
NALM6-Luc+ xenograft model
Oral gavage
35 mg/kg
Twice daily for 14 days
The combination of dasatinib and dexamethasone significantly reduced tumor burden and prolonged survival in mice.
Nat Commun. 2023 May 22;14(1):2935.
Mice
BCR-ABL-positive B-cell acute lymphoblastic leukemia model
Oral gavage
10 mg/kg
Once daily for 21 days
Dasatinib treatment significantly extended the survival of mice with XRCC4/Polθ/p53-deficient leukemic B cells, indicating that Dasatinib can selectively eliminate these leukemic cells after inducing G1 DNA damage.
Nat Commun. 2020 Oct 16;11(1):5239
NSG mice
Humanized NSG mice
Oral
50 mg/kg
On day 0, 1 hour before, 5 hours and 8 hours after injection, and twice daily on days 1 and 2 with 10-11 hour intervals
Dasatinib at 50 mg/kg successfully prevented CD19-TCB-mediated B cell depletion and cytokine release within 48 hours.
J Immunother Cancer. 2021 Jul;9(7):e002582.
Mice
Db/db mice
Oral gavage
5 mg/kg
Once per week for four weeks
Dasatinib reduced lipid accumulation in the heart and bone marrow of diabetic mice, improved diastolic function, and attenuated cardiac fibrosis.
Cardiovasc Diabetol. 2023 Aug 17;22(1):214.
Mice
PS125 mouse Shh MB model
Oral
15 mg/kg
Once daily for 5 consecutive days per week for 4 weeks
Dasatinib significantly inhibited PS125 tumor growth in mice and induced tumor regression.
Cancer Lett. 2014 Nov 1;354(1):68-76.
Mice
Humanized BC CML mouse model
Oral
50 mg/kg
Daily for two weeks
Dasatinib alone or in combination with SAR302503 significantly inhibited BC LSC survival and self-renewal potential
Cell Stem Cell. 2016 Aug 4;19(2):177-191.
Mice
SUP-B15ffLuc xenograft model
Oral
2.5 mg/kg
Daily doses throughout the full treatment duration
To evaluate the effect of Dasatinib on leukemia cell expansion in the SUP-B15ffLuc xenograft model, results showed that Dasatinib alone modestly delayed leukemia expansion, but the combination with PP242 caused regression of leukemic disease.
Nat Med. 2010 Feb;16(2):205-13.
Dasatinib monohydrate/达沙替尼（一水合物） 动物研究
Animal study
The pharmacokinetic profile of Dasatinib monohydrate at 10 mg/kg is suitable for further in vivo efficacy studies, displaying favorable half-lives for both intravenous and oral administration, at 3.3 and 3.1 hours, respectively. The oral bioavailability observed in this study is 27%. At doses of 5 mg/kg and 50 mg/kg, administered once daily for 10 days with a 5 days on and 2 days off schedule, Dasatinib monohydrate demonstrates effective antitumor activity and high safety in a K562 CML xenograft model, resulting in complete tumor regression and low toxicity at multiple dose levels[1].
Jordan
... 展开 >> King Hussein Cancer Center (KHCC)
Not yet recruiting
Amman, Jordan, 11941
Jordan University Hospital (JUH)
Not yet recruiting
Amman, Jordan, 11942
Lebanon
American University of Beirut Medical Center (AUBMC)
Not yet recruiting
Beirut, Lebanon
Saudi Arabia
The King Faisal Specialist Hospital and Research Centre (KFSH&RC)
Not yet recruiting
Riyadh, Saudi Arabia
Tunisia
Aziza Othmana Hospital
Not yet recruiting
Tunis, Tunisia, 1006 收起 <<
Germany
... 展开 >> University Hospital Regensburg, Department of Pediatric Hematology and Oncology
Recruiting
Regensburg, Germany, 93053
Contact: Selim Corbacioglu, MD +49(0)941 944-2101 selim.corbacioglu@ukr.de
Principal Investigator: Selim Corbacioglu, MD 收起 <<
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