Synonym
FB23-2; FB-23-2; FB 23-2; FB232; FB-232; FB 232;
IUPAC/Chemical Name
2-((2,6-dichloro-4-(3,5-dimethylisoxazol-4-yl)phenyl)amino)-N-hydroxybenzamide
InChi Key
ILHNIWOZZKIBNW-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H15Cl2N3O3/c1-9-16(10(2)26-23-9)11-7-13(19)17(14(20)8-11)21-15-6-4-3-5-12(15)18(24)22-25/h3-8,21,25H,1-2H3,(H,22,24)
SMILES Code
O=C(NO)C1=CC=CC=C1NC2=C(Cl)C=C(C3=C(C)ON=C3C)C=C2Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
FB23-2 is a potent and selective inhibitor of mRNA N6-methyladenosine (m6A) demethylase FTO, with an IC50 of 2.6 μM.
In vitro activity:
This study further characterized the effects of FB23-2 on AML cells. FB23-2 substantially accelerated all-trans retinoic acid (ATRA)-induced myeloid differentiation in NB4 and MONOMAC6 cells in a dose-dependent manner (Figures 4A and 4B). Furthermore, FB23-2 induced apoptosis (Figures 4C and 4D) and cell cycle arrest at G1 stage in AML cells (Figures 4E and 4F). Collectively, these results suggest that FB23-2 exhibits FTO-dependent activity in AML cells.
Reference: Cancer Cell. 2019 Apr 15; 35(4): 677–691.e10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812656/
In vivo activity:
Notably, FB23-2 injection substantially delayed the onset of full-blown leukemic symptoms and significantly prolonged survival by almost doubling the median survival (Figure 7C). Compared with the vehicle, FTO inhibitor treatment suppressed leukemia malignancy, including reduced splenomegaly and hepatomegaly (Figure 7D). FACS analysis confirmed that FB23-2 injection suppressed the abundance of human AML cells in the recipient mice (Figures 7E and S5C). As determined by FACS, FB23-2 treatment promoted AML cell differentiation in vivo (Figures 7F and 7G). Wright-Giemsa staining of PB smears revealed that leukemic blasts from FTO inhibitor-treated AML mice were inhibited and partially differentiated; consistently, H&E staining of spleen and liver also showed less AML cell dissemination in FB23-2-treated mice (Figure 7H). Taken together, these data suggests that pharmacological inhibition of FTO by FB23-2 substantially suppresses leukemia progression and prolongs survival.
Reference: Cancer Cell. 2019 Apr 15; 35(4): 677–691.e10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812656/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
70.3 |
179.10 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
392.24
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Huang Y, Su R, Sheng Y, Dong L, Dong Z, Xu H, Ni T, Zhang ZS, Zhang T, Li C, Han L, Zhu Z, Lian F, Wei J, Deng Q, Wang Y, Wunderlich M, Gao Z, Pan G, Zhong D, Zhou H, Zhang N, Gan J, Jiang H, Mulloy JC, Qian Z, Chen J, Yang CG. Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia. Cancer Cell. 2019 Apr 15;35(4):677-691.e10. doi: 10.1016/j.ccell.2019.03.006. PMID: 30991027; PMCID: PMC6812656.
In vitro protocol:
1. Huang Y, Su R, Sheng Y, Dong L, Dong Z, Xu H, Ni T, Zhang ZS, Zhang T, Li C, Han L, Zhu Z, Lian F, Wei J, Deng Q, Wang Y, Wunderlich M, Gao Z, Pan G, Zhong D, Zhou H, Zhang N, Gan J, Jiang H, Mulloy JC, Qian Z, Chen J, Yang CG. Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia. Cancer Cell. 2019 Apr 15;35(4):677-691.e10. doi: 10.1016/j.ccell.2019.03.006. PMID: 30991027; PMCID: PMC6812656.
In vivo protocol:
1. Huang Y, Su R, Sheng Y, Dong L, Dong Z, Xu H, Ni T, Zhang ZS, Zhang T, Li C, Han L, Zhu Z, Lian F, Wei J, Deng Q, Wang Y, Wunderlich M, Gao Z, Pan G, Zhong D, Zhou H, Zhang N, Gan J, Jiang H, Mulloy JC, Qian Z, Chen J, Yang CG. Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia. Cancer Cell. 2019 Apr 15;35(4):677-691.e10. doi: 10.1016/j.ccell.2019.03.006. PMID: 30991027; PMCID: PMC6812656.
1: Huang Y, Su R, Sheng Y, Dong L, Dong Z, Xu H, Ni T, Zhang ZS, Zhang T, Li C,
Han L, Zhu Z, Lian F, Wei J, Deng Q, Wang Y, Wunderlich M, Gao Z, Pan G, Zhong D,
Zhou H, Zhang N, Gan J, Jiang H, Mulloy JC, Qian Z, Chen J, Yang CG.
Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia.
Cancer Cell. 2019 Apr 15;35(4):677-691.e10. doi: 10.1016/j.ccell.2019.03.006.
PubMed PMID: 30991027.
2: Van Der Werf I, Jamieson C. The Yin and Yang of RNA Methylation: An Imbalance
of Erasers Enhances Sensitivity to FTO Demethylase Small-Molecule Targeting in
Leukemia Stem Cells. Cancer Cell. 2019 Apr 15;35(4):540-541. doi:
10.1016/j.ccell.2019.03.011. PubMed PMID: 30991023.
