1. A computer program embodied in a computer-readable storage medium, the computer program implementing a method for migrating a source virtual machine (VM) installed on a source computer to a destination computer, the method comprising:
transferring state information from the source computer to the destination computer, including:
(a) transferring non-memory source VM state information to the destination computer, thereby enabling execution of a destination VM from the transferred non-memory source VM state; and
(b) iteratively transferring source VM memory to the destination VM on the destination computer while the source VM is executing on the source computer, wherein iteratively transferring includes retransferring to the destination computer any units of the source VM memory that were modified since the source VM memory was previously transferred from the source computer to the destination computer.
2. The computer program of claim 1, wherein the retransferring of the units of the source VM memory that were modified is executed a plurality of times.
3. The computer program of claim 2, wherein each subsequent retransferring involves a lesser number of the units than a preceding retransferring.
4. The computer program of claim 3, wherein retransferring of the units of the source VM memory that were modified is repeated until the number of the units is less than a threshold value, and then transferring the number of units after suspending the source VM.
5. The computer program of claim 1, the method further comprising:
executing the destination VM on the destination computer using the transferred state information.
6. The computer program of claim 5, wherein the retransferring of the units is continued after executing the destination VM from the transferred non-memory source VM state.
7. The computer program of claim 1, wherein the iteratively transferring is executed as transfers of pages of memory of the source VM.
8. The computer program of claim 1, in which the source VM’s non-memory state information includes the contents of a source virtual disk, the method further including:
storing the contents of the source virtual disk in a storage arrangement shared by both the source and destination computers; and
preparing a virtual disk of the destination VM by mapping the virtual disk of the destination VM to the same physical addresses as the source virtual disk in the shared storage arrangement.
9. A virtual computer system comprising:
a source virtual machine (VM) executing on a source computer;
a destination VM configured on a destination computer; and
computer software executing on the source and destination computers, the computer software implementing a method for migrating the source VM to the destination computer, the method comprising:
transferring state information from the source computer to the destination computer, including:
(a) transferring non-memory source VM state information to the destination computer, thereby enabling execution of a destination VM from the transferred non-memory source VM state; and
(b) iteratively transferring source VM memory to the destination VM on the destination computer while the source VM is executing on the source computer, wherein iteratively transferring includes retransferring to the destination computer any units of the source VM memory that were modified since the source VM memory was previously transferred from the source computer to the destination computer.
10. The virtual computer system of claim 9, wherein the retransferring of the units of the source VM memory that were modified is executed a plurality of times.
11. The virtual computer system of claim 10, wherein each subsequent retransferring involves a lesser number of the units than a preceding retransferring.
12. The virtual computer system of claim 11, wherein retransferring of the units of the source VM memory that were modified is repeated until the number of the units is less than a threshold value, and then transferring the number of units after suspending the source VM.
13. The virtual computer system of claim 9, the method further comprising:
executing the destination VM on the destination computer using the transferred state information.
14. The virtual computer system of claim 13, wherein the retransferring of the units is continued after executing the destination VM from the transferred non-memory source VM state.
15. The virtual computer system of claim 9, wherein the iteratively transferring is executed as transfers of pages of memory of the source VM.
16. The virtual computer system of claim 9, in which the source VM’s non-memory state information includes the contents of a source virtual disk, the method further including:
storing the contents of the source virtual disk in a storage arrangement shared by both the source and destination computers; and
preparing a virtual disk of the destination VM by mapping the virtual disk of the destination VM to the same physical addresses as the source virtual disk in the shared storage arrangement.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A compound for inhibiting a Bcl-2 family protein selected from one or more of Bcl-2, Bcl-XL, Bcl-w, Mcl-1, and A1Bfl-1 wherein the compound corresponds to Formula (3):
Z1 is hydrocarbyl, substituted hydrocarbyl, heteroaryl, or heterocyclo; and
Z2 is hydrocarbyl, substituted hydrocarbyl, heteroaryl, or heterocyclo.
2. The compound of claim 1 wherein the Bcl-2 family protein is Mcl-1.
3. A composition comprising a Bcl-2, Bcl-XL, andor Bcl-w inhibitor; and an Mcl-1 andor A1Bfl-1 inhibitor, wherein at least one inhibitor is the compound of claim 1.
4. A method of treating or preventing cancer, the method comprising administering the compound of claim 1.
5. A compound comprising a first fragment selected from SZ1 to SZ31 and a second fragment selected from TA1 to TA15.
6. The compound of claim 5 having the formula selected from SZ31TA2, SZ15TA2, and SZ17TA2.
7. A method of screening for an inhibitor, as described herein.
8. The method of claim 7 comprising contacting a fragment library with a Bcl-2 family protein.
9. The method of claim 8 wherein the Bcl-2 family protein is selected from one or more of Bcl-2, Bcl-XL, Bcl-w, Mcl-1, and A1Bfl-1.
10. The method of claim 9 wherein the Bcl-2 family protein is Mcl-1.
11. The compound of claim 1, wherein Z1 is aryl, substituted aryl, or heteroaryl.
12. The compound of claim 1, wherein Z1 has the formula:
wherein
Z10, Z11, Z12, Z13, and Z14 are independently hydrogen, hydroxyl, protected hydroxyl, halo, hydrocarbyl, substituted hydrocarbyl, heterocyclo, heteroaryl, alkoxy, alkenoxy, alkynoxy, aryloxy, arylalkoxy (heterocyclo)alkoxy, trihaloalkoxy, amino, amido, or cyano, or two of Z10, Z11, Z12, Z13, and Z14, together with the carbon atoms to which they are attached, form a fused carbocyclic (e.g., napthyl) or heterocyclic ring.
13. The compound of claim 1, wherein Z10, Z11, Z12, Z13, and Z14 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, amino, alkoxy, nitro, or trihalomethoxy.
14. The compound of claim 1, wherein Z1 has the formula:
wherein
A is phenyl or a five- or six-membered aromatic carbocyclic or heterocyclic ring wherein from one to three carbon atoms may be replaced by a heteroatom selected from N, O, or S, and wherein A is substituted with Z100 and Z101 through ring carbon atoms or ring heteroatoms, and Z100 and Z101 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroaryl, heterocyclo, alkoxy, alkenoxy, alkynoxy, aryloxy, heterocyclo(alkoxy), or halo.
15. The compound of claim 1, wherein Z1 is substituted or unsubstituted furyl, thienyl, pyridyl, oxazolyl, isoxazolyl, imidazolyl, pyridyl, pyrimidyl, purinyl, triazolyl, or thiazolyl.
16. The compound of claim 1, wherein Z1 is substituted or unsubstituted morpholino, pyran, tetrahydropyran, piperazinyl, piperidinyl, tetrahydropyridinyl, pyrrolidinyl, pyrrolinyl, 1,4-diazepanyl, or azepinyl.
17. The compound of claim 1, wherein Z1 is \u2014(CH2)x\u2014Z102 wherein Z102 is hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxyl, protected hydroxyl, heteroaryl, heterocyclo, amino, amido, alkoxy, aryloxy, cyano, nitro, thiol, or an acetal, ketal, ester, ether, or thioether, and x is 1, 2, or 3.
18. The compound of claim 1, wherein Z1, is hydrocarbyl, substituted hydrocarbyl, heteroaryl, heterocyclo, or has the formula:
wherein
Z10, Z11, Z12, Z13, and Z14 are independently hydrogen, amino, alkoxy, aryl, heteroaryl, heterocyclo, nitro, or trihalomethoxy (e.g., trifluoromethoxy); or Z1 is \u2014(CH2)x\u2014Z102 wherein Z102 is hydrogen, alkyl, substituted alkyl, hydroxyl, protected hydroxyl, heteroaryl, heterocyclo, amino, amido, alkoxy, aryloxy, cyano, nitro, thiol, or an acetal, ketal, ester, ether, or thioether, and x is 1, 2, or 3.
19. The compound of claim 1, wherein Z2 is substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, alkaryl, or aralkyl.
20. The compound of claim 1, wherein Z2 has the formula:
wherein
Z20, Z21, Z22, Z23, and Z24 are independently hydrogen, halo, hydrocarbyl, substituted hydrocarbyl, alkoxy, alkenoxy, alkynoxy, aryloxy, nitro, cyano, amino, or amido, or two of Z20, Z21, Z22, Z23, and Z24, together with the carbon atoms to which they are attached, form a fused carbocyclic or heterocyclic ring.
21. The compound of claim 1, Z20, Z21, Z22, Z23, and Z24 are independently alkyl, substituted alkyl, amino, alkoxy, alkenoxy, alkynoxy, or aryloxy.
22. The compound of claim 1, wherein Z2 is phenyl, substituted phenyl, napthyl, or substituted napthyl.
23. The compound of claim 1, wherein Z2 is \u2014(CH2)x\u2014Z200 wherein Z200 is hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxyl, protected hydroxyl, heteroaryl, heterocyclo, amino, amido, alkoxy, aryloxy, cyano, nitro, thiol, or an acetal, ketal, ester, ether, or thioether, and x is 1, 2, or 3.
24. The compound is of claim 1, wherein Z2 is \u2014(CH2)x\u2014Z200 wherein x is 1, 2, or 3 and Z200 is \u2014N(Z201)(Z202), wherein Z201 and Z202 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, or Z201 and Z202, together with the nitrogen atom to which they are attached, for a substituted or unsubstituted alicyclic, bicyclic, aryl, heteroaryl, or heterocyclic moiety.
25. The compound of claim 1, wherein Z2 is substituted or unsubstituted furyl, thienyl, pyrrolyl, oxazolyl, imidazolyl, pyridyl, pyrimidyl, purinyl, triazolyl, or thiazolyl.
26. The compound of claim 1, wherein Z2 is substituted or unsubstituted morpholino, pyran, tetrahydropyran, piperazinyl, piperidinyl, tetrahydropyridinyl, pyrrolidinyl, pyrrolinyl, 1,4-diazepanyl, or azepinyl.
27. The compound of claim 1, wherein the sulfonyl azide corresponds to Formula (2A) or (2B):
wherein Z22 is hydrogen, halo, alkoxy, alkyl, or substituted alkyl; and
Z201 and Z202 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, or Z201 and Z202 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted alicyclic, bicyclic, aryl, heteroaryl, or heterocyclic moiety.
28. The compound of claim 6 having the formula SZ31TA2.
29. The compound of claim 1, wherein the compound has a selectivity index against Bcl-XL andor Mcl-1 of at least about 15.
30. The compound of claim 1, wherein the compound has a selectivity index against Bcl-XL andor Mcl-1 of at least about 30.
31. The compound of claim 1, wherein the compound has a selectivity index against Bcl-XL andor Mcl-1 of at least about 45.
32. The compound of claim 1, wherein the compound has a selectivity against Bcl-XL andor Mcl-1 of at least about 60.
33. The compound of claim 1, wherein the compound has a ligand efficiency of at least about 0.15.
34. The compound of claim 1, wherein the compound has a ligand efficiency of at least about 0.21.
35. The compound of claim 1, wherein the compound has a ligand efficiency of at least about 0.24.