[CAS NO. 284490-13-7] Forodesinehydrochloride
PRODUCTS SPECIFICATIONS [284490-13-7]
DESCRIPTION [284490-13-7]
Overview
| MDL | MFCD22572762 |
|---|---|
| Molecular Weight | 302.71 |
| Molecular Formula | C11H15ClN4O4 |
| SMILES | O=C1C(NC=C2[C@@H]3N[C@H](CO)[C@@H](O)[C@H]3O)=C2NC=N1.Cl |
9 Publications Citing Use of MCE
- [1]Cell. 2019 Oct 31;179(4):864-879.e19.
- [2]Nat Commun. 2017 Aug 14;8(1):241.
- [3]Nucleic Acids Res. 2020 Sep 25;48(17):e101.
- [4]Biosens Bioelectron. 2020 Dec 1;169:112616.
- [5]Cell Rep. 2020 May 12;31(6):107640.
- [6]Int J Biol Sci. 2023; 19(3):772-788.
- [7]J Biol Chem. 2022 May;298(5):101876.
- [8]bioRxiv. 2019 Oct.
- [9]Nat Metab. 2020 Jul;2(7):635-647.
Summary
Forodesine hydrochloride (BCX-1777 hydrochloride) is a highly potent and orally active purine nucleoside phosphorylase (PNP) inhibitor with IC 50 values ranging from 0.48 to 1.57 nM for human, mouse, rat, monkey and dog PNP . Forodesine hydrochloride is a potent human lymphocyte proliferation inhibitor. Forodesine hydrochloride could induce apoptosis in leukemic cells by increasing the dGTP levels [1] [2] .
IC50 & Target
IC50: 1.19 nM (Human PNP), 0.48 nM (Mouse PNP), 1.24 nM (Rat PNP), 0.66 nM (Monkey PNP) and 1.57 nM (Dog PNP) [2]
In Vitro
Forodesine (10-30 μM; 24 and 48 hours; RPMI-8226, MOLT-4 and 5T33MM cells) treatment is partially inhibition of proliferation
[1]
.
Forodesine (10-30 μM; 24 and 48 hours; RPMI-8226, MOLT-4 and 5T33MM cells) has no effect on the MM cells at 24 hours, while it could reduce the percentage of living cells in the MOLT-4 cells with 40%
[1]
.
Forodesine (BCX-1777), in the presence of 2'-deoxyguanosine (dGuo, 3-10 μM), inhibits human lymphocyte proliferation activated by various agents such as interleukin-2 (IL-2), mixed lymphocyte reaction (MLR) and phytohemagglutinin (PHA) (IC
50
values < 0.1-0.38 μM)
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay [1]
| Cell Line: | Human RPMI-8226, human MOLT-4 (T-ALL) cells, 5T33MM (Multiple myeloma, MM). |
| Concentration: | 10 μM, 20 μM, 30 μM |
| Incubation Time: | 24 and 48 hours |
| Result: | At the effects at 48 hours, a complete block in proliferation in the MOLT-4 cells and 15% reduction in the 5T33MM cells. |
Apoptosis Analysis [1]
| Cell Line: | Human RPMI-8226, human MOLT-4 (T-ALL) cells, 5T33MM (Multiple myeloma, MM). |
| Concentration: | 10 μM, 20 μM, 30 μM |
| Incubation Time: | 24 and 48 hours |
| Result: | A limited induction of apoptosis. |
In Vivo
Forodesine (BCX-1777) has excellent oral bioavailability (63%) in mice
[2]
.
At a single dose of 10 mg/kg in mice, Forodesine elevates dGuo to approximately 5 μM
[2]
.
n the human peripheral blood lymphocyte severe combined immunodeficiency (hu-PBL-SCID) mouse model, Forodesine is effective in prolonging the life span 2-fold or more
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00073944 | BioCryst Pharmaceuticals|National Cancer Institute (NCI) |
Cancer
|
April 2003 | Phase 1 |
| NCT00061880 | BioCryst Pharmaceuticals|National Cancer Institute (NCI) |
Lymphoma
|
February 2003 | Phase 1|Phase 2 |
| NCT00095381 | BioCryst Pharmaceuticals |
Leukemia, T-Cell
|
March 2004 | Phase 2 |
| NCT00419081 | BioCryst Pharmaceuticals |
Leukemia|Lymphoma
|
July 2006 | Phase 2 |
| NCT00098332 | BioCryst Pharmaceuticals|National Cancer Institute (NCI) |
Lymphoma
|
November 2004 | Phase 1 |
| NCT00035022 | BioCryst Pharmaceuticals |
Leukemia, Lymphocytic|Lymphoma
|
August 2001 | Phase 1|Phase 2 |
| NCT01776411 | Mundipharma K.K. |
Recurrent or Refractory PTCL
|
January 2013 | Phase 1|Phase 2 |
| NCT00289549 | BioCryst Pharmaceuticals |
Leukemia, Lymphocytic, Chronic
|
June 2005 | Phase 2 |
| NCT00289562 | BioCryst Pharmaceuticals |
B-cell Acute Lymphoblastic Leukemia
|
September 2004 | Phase 1|Phase 2 |
| NCT00823355 | Mundipharma K.K. |
Recurrent or Refractory T+NK-cell Malignancies
|
January 2009 | Phase 1 |
| NCT00742495 | Mundipharma Research Limited|Innovative Therapies For Children with Cancer Consortium |
Relapsed or Refractory T-cell Acute Lymphoblastic Leukaemia|B-cell Precursor Acute Lymphoblastic Leukaemia|T-cell Non-Hodgkin´s Lymphoma
|
March 2009 | Phase 1|Phase 2 |
| NCT00646165 | Mundipharma Research Limited |
B-cell Chronic Lymphocytic Leukemia
|
July 2008 | Phase 1 |
| NCT00501735 | BioCryst Pharmaceuticals |
Cutaneous T-cell Lymphoma (CTCL),
|
July 2007 | Phase 2 |
| NCT00640523 | BioCryst Pharmaceuticals |
Chronic Lymphocytic Leukemia (CLL)
|
March 2008 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
H 2 O : 100 mg/mL ( 330.35 mM ; Need ultrasonic)
DMSO : 10 mg/mL ( 33.03 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.3035 mL | 16.5175 mL | 33.0349 mL |
| 5 mM | 0.6607 mL | 3.3035 mL | 6.6070 mL |
| 10 mM | 0.3303 mL | 1.6517 mL | 3.3035 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 36.67 mg/mL (121.14 mM); Clear solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 5% DMSO >> 95% (20% SBE-β-CD in saline)
Solubility: ≥ 0.5 mg/mL (1.65 mM); Clear solution
References
- [1] Bieghs L, et al. The effects of forodesine in murine and human multiple myeloma cells. Adv Hematol. 2010;2010:131895.
- [2] Bantia S, et al. Purine nucleoside phosphorylase inhibitor BCX-1777 (Immucillin-H)--a novel potent and orally active immunosuppressive agent. Int Immunopharmacol. 2001 Jun;1(6):1199-210.
