Homocarbonyltopsentin (PK4C9) is a small molecule compound that binds TSL2 and is a high carbonyl-forming protein. It binds to the pentaloop conformation of TSL2 and promotes the transition to the clover conformation, enhancing SMN2 exon 7 (E7) splicing with EC50 of 16 μM.

Physicochemical Properties

Molecular Formula	C21H14N4O3
Molecular Weight	370.36086
Exact Mass	370.106
CAS #	172286-77-0
PubChem CID	11326167
Appearance	White to yellow solid powder
LogP	3.3
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	629
Defined Atom Stereocenter Count	0
InChi Key	DRCVQVIMGSWRLN-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H14N4O3/c26-11-5-6-13-15(9-23-17(13)7-11)20(28)21-24-10-18(25-21)19(27)14-8-22-16-4-2-1-3-12(14)16/h1-10,22-23,26H,(H,24,25)
Chemical Name	[2-(6-hydroxy-1H-indole-3-carbonyl)-1H-imidazol-5-yl]-(1H-indol-3-yl)methanone
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	When homocarbonyltopsentin (PK4C9) (10–40 μM) was applied for 24 hours, GM03813C cells expressed SMN2 isoforms, except for E7, up to 5.2 times less frequently than E7, and up to 3 times more frequently than E7 [1]. Homocarbonyltopsentin (PK4C9) (40 μM; 24 hours) increased SMN protein expression 1.5 times over GM03813C cells treated with DMSO [1].
Cell Assay	RT-PCR[1] Cell Types: GM03813C (SMA) cells; GM03814B Fibroblast Tested Concentrations: 10-40 μM Incubation Duration: 24 hrs (hours) Experimental Results: E7 inclusion rate reached a maximum of 91% (DMSO-treated cells increased by 25%). Western Blot Analysis[1] Cell Types: GM03813C (SMA) cells; GM03814B fibroblast Tested Concentrations: 40 μM Incubation Duration: 24 hrs (hours) Experimental Results: SMN protein increased in SMA cells.
References	[1]. Garcia-Lopez A, et al. Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes. Nat Commun. 2018 May 23;9(1):2032.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~337.51 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7001 mL	13.5004 mL	27.0008 mL
	5 mM	0.5400 mL	2.7001 mL	5.4002 mL
	10 mM	0.2700 mL	1.3500 mL	2.7001 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.