TABLE 1.

Small molecular agents examined in vitro.

Molecule	Classification	Molecular Weight	Working Concentrations	Cell lineage/Specimen	Delivery Methods	Primary Osteogenic Effect(s)	References
Tivantinib	3-alkylindoles	369.4 g/mol	50 nM, 200 nM	17IA4 mouse dental pulp cells	Pulp cell culture using standard culture medium treated with tivantinib	Axin2 and Wnt/β-catenin pathway upregulation	Birjandi et al. (2020)
Tideglusib	Naphthalenes	334.4 g/mol	50 nM	Rat dental pulp cells	Pulp cell culture using α-MEM medium treated with tideglusib	Promote odontoblast-like cell differentiation; ALP-positive calcified nodules in isolated rat dental pulp cells	Masuda et al. (2020)
Purmorphamine	Purine	520.6 g/mol	2 μM	Human DPSCs from soft tissue of extracted third molar	β-TCP granules cell-scaffolds cultured in stem cell growth or osteogenic media	Increased ALP activity; OPN , OCN upregulation; stem cell proliferation	Rezia Rad et al. (2016)
Chemical cocktail*	Assortment (see footnote)	Assortment (see footnote)	Assortment (see footnote)	Human DPSCs from soft tissue of extracted third molars, donated human SCAPs, donated GMSCs	Stem cell culture using standard medium treated with chemical cocktail	NeuN, NFM, NSE, MAP2 expression in DPSCs and SCAPs; Musashi1, βIII-Tubulin, NGN2, MASH1 expression in GMSCs	Heng et al. (2019)
Dimethyloxalylglycine	Glycine derivative	175.1 g/mol	1% w/w of PLGA	Human PDLSCs from periodontal ligament of extracted premolars	Stem cells were inoculation using α-MEM growth medium treated with DMOG	Increased ALP activity; Runx2 , OPN, OCN, BSP expression	Shang et al. (2021)
Citrate	Tricarboxylic acids	189.1 g/mol	200 μM	Human MSCs from bone marrow of healthy, non-diabetic adults	Stem cells treated with an osteogenic medium supplemented with pH-adjusted citrate	Increased ALP activity; OPN, Runx2, Col1a1, SPP1 expression; higher calcium/protein ratios	Ma et al. (2018)
Fluoride	Halogen	19 g/mol	Different concentrations between 0 ppm and 200 ppm	Tendons extracted from tails of 12–18 week old Sprague Dawley rats	Rat tendons mineralized in 50 mM Tris buffer with 0, 0.5, 1, 2,	Enhanced crystallization and rod-like mineralization	Saxena et al. (2018)
SB431542	Benzamides	384.4 g/mol	100 μM	Human iPSC-MSCs yielded from sub-culture of bone marrow hiPSCs in MSC medium	Stem cell culture using standard medium, then osteogenic medium after cells attached to CPC scaffold	Promotes stem cell proliferation, differentiation, and viability	Song et al. (2021)
.	.	.	10 μM	Human PObs obtained from child calvarial bone graft patients and mouse PObs harvested from the skulls of mice; Mouse DM cells harvested from dural membrane of mice	Calvarial cell culture using osteogenic differentiation medium treated with SB431542	Increased BMP signaling; increased OCN and Runx2 expression; reduction in activity of Caspase 3; upregulated Smad6	Senarath-Yapa et al. (2016)
Resveratrol	Stilbenes	228.2 g/mol	1.0 mg/ml	Mouse MSCs isolated from bone marrow flushes of female FVB mice	Stem cells were inoculated in growth medium with RSV and RSV-SrRn scaffolds	Increased BMP2 signaling; osteoblastic differentiation; Wnt/β-cateninsignaling upregulation; mineralization in mouse MSCs; angiogenesis	Zhang et al. (2020)
Strontium ranelate	Tetracarboxylic acids	513.5 g/mol	1.0 mg/ml	Mouse MSCs isolated from bone marrow flushes of female FVB mice	Stem cells were inoculated in growth medium with SrRn and RSV-SrRn scaffolds	Increased ALP activity; Inhibited degenerative osteoclast activity	Zhang et al. (2020)
ML323	-	384.5 g/mol	10 μM	Human DPSCs from soft connective tissue of third molars	Stem cells were inoculated in osteogenic differentiation medium treated with ML323	Increased ALP activity; increased calcium accumulation; enhanced osteodifferentiation	Kim and Choung. (2020)
6-Bromoindirubin-3'-	Indole derivative	356.2 g/mol	200 nM, 400 nM, 800 nM	Human DPSCs from soft connective tissue of third molars Oxime	Stem cells were cultured using DMEM growth medium treated with BIO	Increased of ALP activity; ANKH, ENPP1, RUNX2, OSX, OCN, DSPP, DMP1, and OPG expression; RANKL downregulation; enhanced osteoblastic differentiation and mineralized nodule formation	Chatvadee et al. (2022)

*Valproic acid (Propylpentanoic acid derivative; 144.2 g/mol; 0.5 mM), Forskolin (Labdane diterpenoids; 410.5 g/mol; 10 μM), SP600125 (Anthrapyrazoles; 220.2 g/mol; 10 μM), GO6983 (Maleimides; 442.5 g/mol; 5 μM), Y-27632 (N-arylamides; 247.3 g/mol; 5 μM), Repsox (Pyrazolopyridine.; 287.3 g/mol; 1 μM), CHIR99021 (Aminopyrimidines; 465.3 g/mol; 3μM), Dorsomorphin (Pyrazolopyridine; 399.5 g/mol; 1 μM).