Ron Silva built a 501" SB with a race block and a 4.5" (rifle drilled) stroke.

Rod angularity is gonna be pretty severe at 4.5" I don't think I'd try it with a stock block

But opinions vary.

I built a 4.25" stroke as a cruiser that I'll nail only on occasion. For a bracket car I for one will trade away more cubes in exchange for more RPM/Gear and go easier on the block.

Dad always used to say "Just because you CAN, doesn't (always) mean you SHOULD!"