Claims
- 1. A cytotoxic agent comprising one or more maytansinoids linked to a hormone or growth factor via a linking group comprising a disulfide group.
- 2. The cytotoxic agent of claim 1, wherein the maytansinoid is a maytansinoid ester.
- 3. The cytotoxic agent of claim 2, wherein the maytansinoid ester is a C-3 maytansinoid ester.
- 4. The cytotoxic agent of claim 3, wherein the maytansinoid ester is an N-methyl-alanine-containing maytansinoid ester.
- 5. The cytotoxic agent of claim 4, wherein the N-methyl-alanine-containing maytansinoid ester is represented by formula (I): ##STR7## wherein: l represents an integer of 1 to 10; and
- may represents a maytansinoid.
- 6. The cytotoxic agent of claim 4, wherein the N-methyl-alanine-containing maytansinoid ester is represented by formula (II): ##STR8## wherein: R.sub.1 and R.sub.2, which may be the same or different, represents H, CH.sub.3 or CH.sub.2 CH.sub.3 ;
- m represents 0, 1, 2 or 3; and
- may represents a maytansinoid.
- 7. A cytotoxic agent of claim 4, wherein the N-methyl-alanine-containing maytansinoid ester is represented by formula (III): ##STR9## wherein: n represents an integer of 3 to 8; and
- may represents a maytansinoid.
- 8. The cytotoxic agent of claim 4, wherein the N-methyl-alanine-containing maytansinoid ester is a C-3 ester of maytansinol.
- 9. The cytotoxic agent of claim 8, wherein the maytansinoid ester is an ester of dechloro maytansinol.
- 10. The cytotoxic agent of claim 8, wherein the C-3 ester of maytansinol is represented by formula (IV): ##STR10## wherein: l represents 1, 2 or 3;
- Y.sub.0 represents Cl or H; and
- X.sub.3 represents H or CH.sub.3.
- 11. The cytotoxic agent of claim 8, which comprises N-methyl-N-(3-methyldithiopropanoyl)-L-alanine.
- 12. The cytotoxic agent of claim 3, wherein the maytansinoid ester is an N-methyl-cysteine-containing maytansinoid ester.
- 13. The cytotoxic agent of claim 12, wherein the N-methyl-cysteine-containing maytansinoid ester is represented by formula (V): ##STR11## wherein: o represents 1, 2 or 3;
- p represents O or an integer of 1 to 10; and
- may represents a maytansinoid.
- 14. The cytotoxic agent of claim 12, wherein the N-methyl-cysteine-containing ester is a C-3 ester of maytansinol.
- 15. The cytotoxic agent of claim 14, wherein the maytansinoid ester is an ester of dechloro maytansinol.
- 16. The cytotoxic agent of claim 12, wherein the N-methyl-cysteine-containing maytansinoid ester is represented by formula (VI): ##STR12## wherein: o represents 1, 2, or 3;
- q represents O or an integer of 1 to 10;
- Y.sub.0 represents Cl or H; and
- X.sub.3 represents H or CH.sub.3.
- 17. The cytotoxic agent of claim 1, wherein said hormone is melanocyte stimulating hormone (MSH) or an analogue thereof.
- 18. The cytotoxic agent of claim 1, wherein said hormone is thyroid stimulating hormone (TSH) or an analogue thereof.
- 19. The cytotoxic agent of claim 1, wherein said growth factor is epidermal growth factor (EGF).
- 20. The cytotoxic agent of claim 1, wherein said growth factor is transforming growth factor alpha (TGF-.alpha.).
Parent Case Info
This is a continuation of application Ser. No. 07/911,380 filed Jul. 13, 1992, now U.S. Pat. No. 5,208,020, which is a Continuation of Ser. No. 07/426,247, filed Oct. 25, 1989, (now abandoned).
US Referenced Citations (17)
Foreign Referenced Citations (1)
Number |
Date |
Country |
0205326 |
Dec 1986 |
EPX |
Continuations (2)
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Number |
Date |
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Parent |
911380 |
Jul 1992 |
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Parent |
426247 |
Oct 1989 |
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