ABT-199
ABT-199, developed through a structure-based reverse engineering process, is a novel and specific inhibitor of B-cell lymphoma/leukemia 2 (BCL-2) maintaining a sub-nanomolar affinity towards BCL-2 and over three orders of magnitude less affinity towards BCL-XL. It kills a diverse array of non-Hodgkin lymphoma (NHL) and acute myelogenous leukemia cell lines as well as BCL-2 dependent but not BCL-XL dependent cells via suppressing mitochondrial pathway of apoptosis, exhibiting potent antitumor activity against a wide variety of hematologic malignancies while sparing platelets. According to previous studies, ABT-199 is capable of suppressing tumor growth in several human hematologic tumor xenograft models.
Reference
Matthew S. Davids and Anthony Letai. ABT-199: a new hope for selective BCL-2 inhibition. Cancer Cell 2013; 23(2): 139-141
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 868.44 |
| Cas No. | 1257044-40-8 |
| Formula | C45H50ClN7O7S |
| Synonyms | ABT199, ABT 199, GDC0199, GDC-0199 |
| Solubility | ≥43.42 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
| Chemical Name | 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide |
| SDF | Download SDF |
| Canonical SMILES | CC1(CCC(=C(C1)C2=CC=C(C=C2)Cl)CN3CCN(CC3)C4=CC(=C(C=C4)C(=O)NS(=O)(=O)C5=CC(=C(C=C5)NCC6CCOCC6)[N+](=O)[O-])OC7=CN=C8C(=C7)C=CN8)C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
normal human B cells, as well as CD4+ and CD8+ T cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
24 h; 4 μM |
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Applications |
We first determined the in vitro sensitivity to ABT-199 of normal human B cells, as well as CD4+ and CD8+ T cells in peripheral blood sampled from healthy donors (n=9). Significantly, normal peripheral B cells were intrinsically more sensitive (~1000 fold) to ABT-199 than either T cell subset (mean ABT-199 LC50±s.e.m. for B cells, CD4 T cells and CD8 T cells were 3.0±0.9 nM, 2.5±0.6 μM and 1.3±0.7 μM , respectively; B versus CD4 T cells: P=0.008; and B versus CD8 T cells: P=0.004). The result shown that normal human peripheral blood B cells are highly sensitive to ABT-199, unlike T cells and myeloid cells. |
| Animal experiment [1]: | |
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Animal models |
Eμ-Myc mice |
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Dosage form |
100 mg/kg; Oral taken |
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Applications |
We examined the effect of short-term treatment with ABT-199 (used at 100 mg/kg) on the lymphoid subpopulations in vivo to assess this and to model probable changes during therapy of patients. ABT-199 was administered orally, Consistent with our in vitro observations with murine and human cells, the drug substantially reduced peripheral B cells to a similar extent. These data suggested that because of intrinsic insensitivity to selective Bcl-2 inhibition of key B- and T-precursor cells, longer-term administration of ABT-199 may have an impact on normal lymphopoiesis to a lesser degree. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Khaw S L, Mérino D, Anderson M A, et al. Both leukaemic and normal peripheral B lymphoid cells are highly sensitive to the selective pharmacological inhibition of prosurvival Bcl-2 with ABT-199[J]. Leukemia, 2014, 28(6): 1207-1215. |
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| ABT-199 (GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM, >4800 fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. | ||||||
| Targets | Bcl-2 | |||||
| IC50 | < 0.010 nM (Ki) | |||||
Quality Control & MSDS
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