XIAP/cIAP1 antagonist-1 is a potent and orally bioactive XIAP/cIAP1 antagonist (inhibitor) with EC50s of 5.1 nM and 0.32 nM for XIAP and cIAP1, respectively. XIAP/cIAP1 antagonist-1 inhibits tumor growth in a dose-dependent fashion in vivo.

Physicochemical Properties

Molecular Formula	C29H40FN5O2
Molecular Weight	509.67
Exact Mass	509.316
CAS #	1403898-55-4
PubChem CID	135397708
Appearance	White to off-white solid powder
Density	1.1±0.1 g/cm3
Boiling Point	678.3±55.0 °C at 760 mmHg
Flash Point	364.0±31.5 °C
Vapour Pressure	0.0±2.1 mmHg at 25°C
Index of Refraction	1.549
LogP	4.23
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	37
Complexity	775
Defined Atom Stereocenter Count	3
SMILES	C[C@H]1CN([C@@H](CN1)CN2CCOC[C@@H]2C)CC(=O)N3CC(C4=C3C=C(C=N4)CC5=CC=C(C=C5)F)(C)C
InChi Key	XIQKDUKFFKQZAO-WATLYSKOSA-N
InChi Code	InChI=1S/C29H40FN5O2/c1-20-15-34(25(14-31-20)16-33-9-10-37-18-21(33)2)17-27(36)35-19-29(3,4)28-26(35)12-23(13-32-28)11-22-5-7-24(30)8-6-22/h5-8,12-13,20-21,25,31H,9-11,14-19H2,1-4H3/t20-,21-,25-/m0/s1
Chemical Name	1-[6-[(4-fluorophenyl)methyl]-3,3-dimethyl-2H-pyrrolo[3,2-b]pyridin-1-yl]-2-[(2S,5S)-5-methyl-2-[[(3S)-3-methylmorpholin-4-yl]methyl]piperazin-1-yl]ethanone
Synonyms	AT-IAP ATIAP AT IAP
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Compound 26 (XIAP/cIAP1 antagonist-1) exhibited antiproliferative action in MDA-MB-231 cells, with an IC50 of 4.4 nM [1].
ln Vivo	Tumor growth is inhibited in a dose-dependent manner by XIAP/cIAP1 antagonist-1 (compound 26) (7.5, 15, 30 mg/kg; oral; administered daily for 24 days) [1]. The oral bioavailability of XIAP/cIAP1 Antagonist-1 is 5 mg/kg (F=22%) when administered intravenously (1 mg/kg; 5, 30 mg/kg orally) [1]. XIAP/cIAP1 antagonist-1 pharmacokinetic characteristics in Balb/c SCID mice [1]. The dosage (in mg/kg), the route, the maximum time (in h), the maximum concentration (in μg/mL), the CLp (in mL/min/kg), the Vss (in L/kg), the half-life (in h), and the AUC (in μg·h/mL) are all presented.
Animal Protocol	Animal/Disease Models: Balb/c SCID (severe combined immunodeficient) mouse carrying MDA-MB-231 xenografts [1] Doses: 7.5, 15, 30 mg/kg Route of Administration: PO; one time/day for 24 days Experimental Results: Inhibited tumor growth in a dose-dependent manner. Animal/Disease Models: Balb/c SCID (severe combined immunodeficient) mouse carrying MDA-MB-231 xenografts [1] Doses: Route of Administration: intravenous (iv) (iv)injection of 1 mg/kg; 5. Oral administration of 30 mg/kg Experimental Results: Shows oral bioavailability ( F=22%).
References	[1]. Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis Protein (XIAP). J Med Chem. 2017; 60(11):4611-4625.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9621 mL	9.8103 mL	19.6205 mL
	5 mM	0.3924 mL	1.9621 mL	3.9241 mL
	10 mM	0.1962 mL	0.9810 mL	1.9621 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.