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MedKoo Cat#: 206570 | Name: ASTX-660
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Tolinapant, also known as ASTX660, is an orally bioavailable, non-peptidomimetic antagonist of both X chromosome-linked inhibitor of apoptosis protein (XIAP) and cellular IAP 1 (cIAP1), with potential antineoplastic and pro-apoptoticctivities. Upon administration, XIAP/cIAP1 antagonist ASTX660 selectively binds to and inhibits the activity of XIAP and cIAP1. This restores and promotes the induction of apoptotic signaling pathways in cancer cells, and inactivates the nuclear factor-kappa B (NF-kB)-mediated survival pathway. XIAP and cIAP1 are overexpressed by many cancer cell types and suppress apoptosis by inhibiting the activity of certain caspases; they promote both cancer cell survival and chemotherapy resistance.

Chemical Structure

ASTX-660
ASTX-660
CAS#1799328-86-1 (free base)

Theoretical Analysis

MedKoo Cat#: 206570

Name: ASTX-660

CAS#: 1799328-86-1 (free base)

Chemical Formula: C30H42FN5O3

Exact Mass: 539.3272

Molecular Weight: 539.70

Elemental Analysis: C, 66.77; H, 7.84; F, 3.52; N, 12.98; O, 8.89

Price and Availability

Size Price Availability Quantity
1mg USD 80.00 Ready to ship
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,250.00 Ready to ship
200mg USD 2,050.00 Ready to ship
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Related CAS #
1799328-86-1 (free base) 1799328-50-9 (HCl) 1799328-90-7 (mesylate) 1799328-88-3 (sulfate)
Synonym
ASTX660; ASTX-660; ASTX 660; Tolinapant;
IUPAC/Chemical Name
1-(6-(4-fluorobenzyl)-5-(hydroxymethyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-((2R,5R)-5-methyl-2-(((R)-3-methylmorpholino)methyl)piperazin-1-yl)ethan-1-one
InChi Key
YCXOHEXZVKOGEV-DNRQZRRGSA-N
InChi Code
InChI=1S/C30H42FN5O3/c1-20-14-35(25(13-32-20)15-34-9-10-39-18-21(34)2)16-28(38)36-19-30(3,4)29-27(36)12-23(26(17-37)33-29)11-22-5-7-24(31)8-6-22/h5-8,12,20-21,25,32,37H,9-11,13-19H2,1-4H3/t20-,21-,25-/m1/s1
SMILES Code
OCC1=NC2=C(N(CC2(C)C)C(CN3[C@@H](CN4[C@H](C)COCC4)CN[C@H](C)C3)=O)C=C1CC5=CC=C(F)C=C5
Appearance
Solid powder
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, not in water
Shelf Life
>2 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
More Info
Related: 1605316-16-2 (ASTX660 2HCl salt) 1605584-14-2 (ASTX660 free base).
Biological target:
ASTX660 is a dual antagonist of cellular inhibitor of apoptosis protein (cIAP) and X-linked inhibitor of apoptosis protein (XIAP).
In vitro activity:
Experiments were performed to evaluate other immune mechanisms by which ASTX660 exerts its anti-tumor immunity at the tumor cell level. We used the xCELLigence impedance platform in three murine tumor cell lines to record cell density over time, previously shown to reflect tumor cell killing mediated by T cells enriched from tumor infiltrating lymphocytes (TIL)41 (Figure 4). Cultured T cells from day 7–14 MOC1, MEER, or MOC2 tumors were magnetically sorted and plated at various effector:target (E:T) ratios with or without ASTX660. In all cell lines, ASTX660 alone was not cytotoxic. TIL added in a 1:1 ratio of effector (TIL) cells to target (tumor) cells had a significant effect in MOC1, moderate effects in MEER, and no effect on tumor cell killing in MOC2. In all cell lines, the addition of ASTX660 enhanced TIL killing of tumor cells. In additional impedance experiments in MEER cells, the addition of MHC class I blocking antibody abrogated ASTX660-induced enhancement of tumor cell killing by T cells (Suppl. Figure S8). Taken together, these data suggest that in addition to immunogenic cell death, ASTX660 is able to enhance tumor cell killing through a process involving MHC class I in an environment devoid of dendritic cells. Reference: Oncoimmunology. 2020; 9(1): 1710398. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959437/
In vivo activity:
The dose- and schedule-dependent antitumor effects of ASTX660 were investigated in the MDA-MB-231 breast cancer xenograft model (Fig. 6A and B; Supplementary Fig. S4A and S4B). Daily oral administration of ASTX660 at 5, 10, and 20 mg/kg significantly inhibited tumor growth (P < 0.05 from days 15, 18, and 11, respectively; Fig. 6A). An intermittent schedule (cycles of 7 consecutive days of dosing followed by 7 days of dose-holiday) at 20 mg/kg also achieved significant tumor growth inhibition, and its effects were equivalent to the continuous schedule in the same model (both P < 0.05 vs. vehicle treatment from day 8; Fig. 6B). The activity of ASTX660 was further investigated in an A375 melanoma xenograft model in nude mice (Fig. 6C; Supplementary Fig. S4C-i). Daily oral administration of ASTX660 at 10 and 20 mg/kg caused significant tumor growth inhibition in an A375. In all three studies, the ASTX660 treatments were well tolerated, and no excessive bodyweight loss or significant adverse effects were observed (Supplementary Fig. S4A-i, S4B-I, and S4C-i). Reference: Mol Cancer Ther. 2018 Jul;17(7):1381-1391. https://pubmed.ncbi.nlm.nih.gov/29695633/
Solvent mg/mL mM
Solubility
DMSO 75.0 138.97
Ethanol 100.0 185.29
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 539.70 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.

Recalculate based on batch purity %
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. Ward GA, Lewis EJ, Ahn JS, Johnson CN, Lyons JF, Martins V, Munck JM, Rich SJ, Smyth T, Thompson NT, Williams PA, Wilsher NE, Wallis NG, Chessari G. ASTX660, a Novel Non-peptidomimetic Antagonist of cIAP1/2 and XIAP, Potently Induces TNFα-Dependent Apoptosis in Cancer Cell Lines and Inhibits Tumor Growth. Mol Cancer Ther. 2018 Jul;17(7):1381-1391. doi: 10.1158/1535-7163.MCT-17-0848. Epub 2018 Apr 25. PMID: 29695633. 2. Ye W, Gunti S, Allen CT, Hong Y, Clavijo PE, Van Waes C, Schmitt NC. ASTX660, an antagonist of cIAP1/2 and XIAP, increases antigen processing machinery and can enhance radiation-induced immunogenic cell death in preclinical models of head and neck cancer. Oncoimmunology. 2020 Jan 9;9(1):1710398. doi: 10.1080/2162402X.2019.1710398. PMID: 32002309; PMCID: PMC6959437.
In vitro protocol:
1. Ward GA, Lewis EJ, Ahn JS, Johnson CN, Lyons JF, Martins V, Munck JM, Rich SJ, Smyth T, Thompson NT, Williams PA, Wilsher NE, Wallis NG, Chessari G. ASTX660, a Novel Non-peptidomimetic Antagonist of cIAP1/2 and XIAP, Potently Induces TNFα-Dependent Apoptosis in Cancer Cell Lines and Inhibits Tumor Growth. Mol Cancer Ther. 2018 Jul;17(7):1381-1391. doi: 10.1158/1535-7163.MCT-17-0848. Epub 2018 Apr 25. PMID: 29695633. 2. Ye W, Gunti S, Allen CT, Hong Y, Clavijo PE, Van Waes C, Schmitt NC. ASTX660, an antagonist of cIAP1/2 and XIAP, increases antigen processing machinery and can enhance radiation-induced immunogenic cell death in preclinical models of head and neck cancer. Oncoimmunology. 2020 Jan 9;9(1):1710398. doi: 10.1080/2162402X.2019.1710398. PMID: 32002309; PMCID: PMC6959437.
In vivo protocol:
1. Ward GA, Lewis EJ, Ahn JS, Johnson CN, Lyons JF, Martins V, Munck JM, Rich SJ, Smyth T, Thompson NT, Williams PA, Wilsher NE, Wallis NG, Chessari G. ASTX660, a Novel Non-peptidomimetic Antagonist of cIAP1/2 and XIAP, Potently Induces TNFα-Dependent Apoptosis in Cancer Cell Lines and Inhibits Tumor Growth. Mol Cancer Ther. 2018 Jul;17(7):1381-1391. doi: 10.1158/1535-7163.MCT-17-0848. Epub 2018 Apr 25. PMID: 29695633. 2. Ye W, Gunti S, Allen CT, Hong Y, Clavijo PE, Van Waes C, Schmitt NC. ASTX660, an antagonist of cIAP1/2 and XIAP, increases antigen processing machinery and can enhance radiation-induced immunogenic cell death in preclinical models of head and neck cancer. Oncoimmunology. 2020 Jan 9;9(1):1710398. doi: 10.1080/2162402X.2019.1710398. PMID: 32002309; PMCID: PMC6959437.
1: Xiao R, An Y, Ye W, Derakhshan A, Cheng H, Yang X, Allen C, Chen Z, Schmitt NC, Van Waes C. Dual Antagonist of cIAP/XIAP ASTX660 Sensitizes HPV- and HPV+ Head and Neck Cancers to TNFα, TRAIL, and Radiation Therapy. Clin Cancer Res. 2019 Nov 1;25(21):6463-6474. doi: 10.1158/1078-0432.CCR-18-3802. Epub 2019 Jul 2. PMID: 31266830; PMCID: PMC6825532.