Table 3.

Antitumor activity of SPH3463 in s.c. human tumor xenografts

Subcutaneous xenograft	Treatment	Method of treatment	Concentration (mg/kg)	TGI (%)	Body weight change (%)
MCF‐7	Vehicle	i.g., QD´21 d	—	—	↑1.6
	SPH3643		12.5	62	↓0.9
			25	82**	↓2.9
			50	96**, a	↓3.3
	LY2835219		50	114**	↓6.0
	Palbociclib		50	84**	↓1.4
MCF‐7/ARO	Vehicle	i.g., QD´21 d	—	—	↑15
	SPH3643		37.5	51*	↓3
			75	60**	↑1
			150	71**	↓4
	LY2835219		150	67**	↓17
	Palbociclib		150	67**	↓11
MCF‐7/ARO	Vehicle	i.g., QD´21 d	—	—	↓1
	SPH3643		75	44**	↓10
	LY2835219		75	49**	↓12
	Letrozole		20	45**	↓1
	SPH3643 + letrozole		75 + 20	74**,b,c	↓7
	LY2835219 + letrozole		75 + 20	62**	↓13
Colo‐205	Vehicle	i.g., QD´14 d	—	—	↓11
	SPH3643		25	73**	↑2
			50	86**	↑1
			100	99**	↑9
	LY2835219		50	82**	↑5
	Palbociclib		50	93**	↑8
MV4‐11	Vehicle	i.g., QD´20 d	—	—	↑21
	SPH3643		12.5	11	↑9
			25	31*	↑6
			50	56**, #	↑3
	LY2835219		50	54**, #	↑5
	Palbociclib		50	68**	↑3
U87‐MG	Vehicle	i.g., QD´18 d	—	—	↑10
	SPH3643		12.5	70**	↑6
			25	88**	↑7
			50	139**,##	↑5
	LY2835219		50	131**,##	↓2
	Palbociclib		50	96**	↑6

*P < .05, treatment vs vehicle; **P < .01, treatment vs vehicle; #P < .05, treatment vs palbociclib in U87‐MG or MV4‐11 cells; ##P < .01, treatment vs palbociclib in U87‐MG or MV4‐11 cells.

^aSPH3643 50 mg/kg vs LY2835219 50 mg/kg.

^bSPH3643 + letrozole vs SPH3643 75 mg/kg.

^cSPH3643 + letrozole vs LY2835219 + letrozole.

—, not applicable; i.g., intragastric administration; QD, once daily; TGI, the tumor growth inhibition value.