When I was a younger man I used a 404 Jeffery for many months. It was an old original rifle made my Jeffery
The 404 was designed to be a bolt action replacement for the 450/400 as I was told.
Both fired 400 grain bullets of about the same diameter at about the same velocity. I used 2 different kinds of ammo back then. Old Kynoch which was loaded to about 2150 FPS and some German ammo (which may have been DWM or RWS, but I can’t remember now) which I was told was loaded to 2350 FPS.

I can tell you faithfully, the 404 was a super good all-around gun and worked very well on every animal I used it against from the smallest to the very largest. I am speaking for weights from about 75 pounds to about 10,000 pounds.
So I can't see why the 450/400would not be a superb rifle for all uses except for animals under about 30 pounds (thing 22 LR or maybe 222 here) and for any long range shots of about 300 yards or more. ( Think scoped bolt action in a flat shooting caliber here)

Iron sights are the sights of either (A) good eyes or (B)disciplined sportsmen.
When I was young I had 20/10 vision, or what the military doctor called "double perfect".
I never felt the slightest bit handicapped with that old rifle at any range I ever had an opportunity to shoot.
Now days, I would need a good peep sight, ---- and a scope is worth the price, with no arguments.

I am a firm believer that the "very best" caliber for "one rifle for everything" is still the 375H&H, but I would feel "good" about it also with a 450/400, or a 404, or a 416 Taylor or any of the 416s for that matter.

I don't believe I would load any of the 40-42 calibers to more then 2250 FPS. I see no reason to do it. Loaded faster gives more range, but I have never seen ANY reason to need additional powder that what I get with my 375 H&H if I am shooting at ANYTHING over 100 yards away. The 375 is a better option for me for longer shots on game then any of the 40+ rifles because I shoot it better, and I have never seen any lack of power from it.
It is not going to be as effective as a 40+ at "stopping” a big animals but at 100 yds or more, I don't really care if the game moves 50-75 yards before it falls. ( an just as a note, I have never had one got more then 20 yds after I shot it with a 375)
No animal is dangerous until it's very close.

At very close range against a wounded dangerous animal, I would move right up to a 458 or one of the 460s or maybe a 505.

So hot loading the 450/400 or 404, or even the 416s doesn't make a lot of sense to me. Long shots is not what I would use these rifles for.
They are great for general purposes, having the ability to do about 95% of all tasks we'd ask of them. They actually have more than enough power for most hunting.

For a BIG wounded animal at very close range, a bigger rifle is going to probably be better, but that nitch is nearly always the rheum of a guide or pro-hunter, backing up a client that didn't do a very good job with the first round.

I have owned and built a lot of very large rifles in my life and shot them too, but I have no particular use any more for anything much larger then a "40" . I have made and owned Bolt actions up to 505 Gibbs, and I have made and shot muzzleloaders up to 4 bore. I made one 2 bore rifle too, but I would not fire it from my shoulder. (I am just not up to that .)

My favorite 2 calibers are still 270 Winchester and 375H&H, but I have a soft spot in my heart for the 404, 450/400 and the 416 Taylor too.
Bottom line is this:
If you like a 450/400 get one. You will not be unhappy.