NPASS Compound

Natural Product: NPC542254

Natural Product ID	NPC542254
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-[(2~{S},3~{S},4~{S},5~{R},6~{S})-3,4-dihydroxy-6-methyl-5-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-2-(3,4-dihydroxyphenyl)-5-hydroxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	3-[(2~{S},3~{S},4~{S},5~{R},6~{S})-3,4-dihydroxy-6-methyl-5-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-2-(3,4-dihydroxyphenyl)-5-hydroxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 114120 0 0 0 0 0 0 0 0999 V2000 9.5097 2.0898 -4.0018 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0522 0.6807 -3.8607 C 0 0 2 0 0 0 0 0 0 0 0 0 8.2253 0.5000 -2.8165 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6730 0.3094 -1.5558 C 0 0 1 0 0 0 0 0 0 0 0 0 7.9380 -0.7481 -0.9652 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9795 -0.3211 -0.1041 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3285 -1.5455 0.5539 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2690 -1.1992 1.3151 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7346 -2.2011 2.0613 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4672 -1.7833 2.5985 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5475 -0.9990 1.9171 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7282 -0.6355 0.6230 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7899 0.1501 -0.0047 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9098 0.5582 -1.3172 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6560 0.5618 0.7086 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2797 1.3472 0.0798 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1461 1.6952 -1.0976 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4022 1.7256 0.8655 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3036 2.5049 0.1546 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3715 1.7994 -0.4771 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8757 0.6590 -1.1780 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9814 -0.2190 -1.2065 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9321 -1.1580 -0.0607 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2611 0.4953 -1.4062 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.2999 -0.2587 -1.8760 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4518 -0.0319 -1.1870 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.7514 -1.0389 -0.2042 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.8237 -0.4334 0.4932 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.8405 -0.7002 1.9573 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6504 -0.1959 2.4852 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.0643 -0.9084 -0.2563 C 0 0 1 0 0 0 0 0 0 0 0 0 -11.0739 0.0044 -0.0344 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.7154 -0.9435 -1.7655 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.2404 -2.2177 -2.0716 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6531 0.0875 -2.0592 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.1467 1.3864 -1.9754 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0650 1.7607 -2.2436 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2382 2.4874 -2.3179 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0630 2.6382 -1.4806 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0964 3.0208 -2.4345 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5754 1.3617 2.1446 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7345 1.7378 2.9843 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9490 1.0368 4.1584 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9872 1.2883 5.0399 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8487 2.3032 4.7096 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8986 2.5598 5.5844 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6665 3.0242 3.5547 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5511 4.0490 3.2490 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6054 2.7395 2.6914 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6260 0.5956 2.6965 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4344 0.2104 2.0307 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4060 -0.5745 2.6039 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6565 -3.5154 1.4336 C 0 0 2 0 0 0 0 0 0 0 0 0 5.2942 -4.5197 2.2302 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1575 -3.6396 0.0549 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0572 -3.6871 -0.8716 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1221 -2.6225 -0.4468 C 0 0 2 0 0 0 0 0 0 0 0 0 7.3802 -3.2167 -0.6896 O 0 0 0 0 0 0 0 0 0 0 0 0 10.1180 0.1137 -1.4367 C 0 0 1 0 0 0 0 0 0 0 0 0 10.4787 -0.4758 -0.1882 O 0 0 0 0 0 0 0 0 0 0 0 0 10.7185 -0.6464 -2.5597 C 0 0 1 0 0 0 0 0 0 0 0 0 10.5968 -2.0040 -2.3300 O 0 0 0 0 0 0 0 0 0 0 0 0 10.1965 -0.3127 -3.9113 C 0 0 1 0 0 0 0 0 0 0 0 0 9.8203 -1.4320 -4.6524 O 0 0 0 0 0 0 0 0 0 0 0 0 10.4262 2.2984 -3.4278 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7153 2.8161 -3.6948 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7344 2.3524 -5.0778 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4489 0.4605 -4.8001 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3426 1.2266 -0.9831 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1952 0.2381 -0.6446 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3575 0.3263 0.7249 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1267 -1.9435 1.2727 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4502 -2.2499 2.9727 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5854 -0.9514 0.0179 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7463 1.0928 -1.5797 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9798 1.3402 0.3107 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8161 -0.8329 -2.1484 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2700 -0.8412 0.7733 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6756 -2.2036 -0.3587 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9721 -1.2416 0.3940 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6285 0.9326 -0.4273 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2495 0.8926 -0.5426 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7198 0.6841 0.3808 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9411 -1.7433 2.2619 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6485 -0.0529 2.3862 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2896 0.5372 1.9009 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3218 -1.9361 0.0501 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.5505 -0.2295 0.7964 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6238 -0.6937 -2.3015 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1414 -2.7682 -1.2421 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3152 -0.1117 -3.1168 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8370 1.4986 -2.6862 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6562 1.5264 -3.2116 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1745 3.3837 -1.8878 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5693 3.5272 -1.0467 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1798 3.9243 -2.7570 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2481 0.2335 4.3947 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0992 0.6863 5.9457 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2585 3.5029 5.7349 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4506 4.5353 2.3789 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5096 3.3484 1.8266 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2833 -0.8781 3.6509 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5403 -3.8478 1.3883 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6949 -4.7660 2.9812 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6583 -4.6632 -0.0810 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4911 -3.6235 -1.7807 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7832 -2.2270 -1.4435 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5436 -3.3533 -1.6583 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6169 1.1189 -1.3782 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6283 -0.8476 0.1589 H 0 0 0 0 0 0 0 0 0 0 0 0 11.8486 -0.4610 -2.5441 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8951 -2.2950 -1.4474 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9969 0.1957 -4.4857 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9418 -1.2140 -5.0803 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 28 31 1 0 31 32 1 0 31 33 1 0 33 34 1 0 33 35 1 0 35 36 1 0 24 37 1 0 37 38 1 0 37 39 1 0 39 40 1 0 18 41 2 0 41 42 1 0 42 43 2 0 43 44 1 0 44 45 2 0 45 46 1 0 45 47 1 0 47 48 1 0 47 49 2 0 41 50 1 0 50 51 1 0 51 52 2 0 9 53 1 0 53 54 1 0 53 55 1 0 55 56 1 0 55 57 1 0 57 58 1 0 4 59 1 0 59 60 1 0 59 61 1 0 61 62 1 0 61 63 1 0 63 64 1 0 63 2 1 0 57 7 1 0 52 11 1 0 51 15 1 0 39 20 1 0 49 42 1 0 35 26 1 0 1 65 1 0 1 66 1 0 1 67 1 0 2 68 1 6 4 69 1 1 6 70 1 0 6 71 1 0 7 72 1 1 9 73 1 1 12 74 1 0 14 75 1 0 20 76 1 1 22 77 1 6 23 78 1 0 23 79 1 0 23 80 1 0 24 81 1 1 26 82 1 1 28 83 1 1 29 84 1 0 29 85 1 0 30 86 1 0 31 87 1 1 32 88 1 0 33 89 1 6 34 90 1 0 35 91 1 6 36 92 1 0 37 93 1 6 38 94 1 0 39 95 1 1 40 96 1 0 43 97 1 0 44 98 1 0 46 99 1 0 48100 1 0 49101 1 0 52102 1 0 53103 1 6 54104 1 0 55105 1 1 56106 1 0 57107 1 6 58108 1 0 59109 1 1 60110 1 0 61111 1 6 62112 1 0 63113 1 6 64114 1 0 M END

Standard InCHIKey	QLLBJLPRDZPFEQ-GXZFEBORSA-N
Standard InCHI	InChI=1S/C39H50O25/c1-10-21(44)25(48)29(52)36(57-10)56-9-19-23(46)27(50)30(53)38(62-19)59-13-6-16(43)20-17(7-13)60-34(12-3-4-14(41)15(42)5-12)35(24(20)47)64-37-32(55)28(51)33(11(2)58-37)63-39-31(54)26(49)22(45)18(8-40)61-39/h3-7,10-11,18-19,21-23,25-33,36-46,48-55H,8-9H2,1-2H3/t10-,11-,18+,19+,21-,22+,23+,25-,26-,27-,28-,29-,30+,31+,32-,33-,36+,37-,38+,39-/m0/s1
SMILES	C[C@@H]1O[C@@H](OC[C@H]2O[C@@H](OC3=CC(O)=C4C(=O)C(O[C@@H]5O[C@@H](C)[C@H](O[C@@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@H]6O)[C@@H](O)[C@@H]5O)=C(C5=CC=C(O)C(O)=C5)OC4=C3)[C@H](O)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	918.26	Volume:	821.869 ? Van der Waals volume.
Dense:	1.117	LogP:	-0.698 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.518 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.455 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	42.0
TPSA:	407.5 ? Topological Polar Surface Area.	H-Bond Acceptor:	25.0
H-Bond Donor:	15.0	Rings:	7.0
Heavy Atoms:	25.0

MedChem Properties

QED Drug-Likeness Score:	0.08	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.952	Fsp³:	0.615
MCE-18:	185.381 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.647	Fluc inhibitor:	0.368 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.768 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.528 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.286	Promiscuous compounds:	0.588

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-7.001	MDCK Permeability:	-4.797
Pgp-inhibitor:	0.0	Pgp-substrate:	0.894
PAMPA:	1.0 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.938
20% Bioavailability (F20%):	0.204	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.002
Plasma Protein Binding (PPB):	63.503%	Volume Distribution (VD):	-0.133
Fu:	28.88% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.034
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.711
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.902
HLM stability:	0.022 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

0.064

Half-life (T1/2):

6.564

ADMET: Toxicity

hERG Blockers:	0.002	hERG Blockers (10um):	0.053
Human Hepatotoxicity (H-HT):	0.49	Drug-induced Liver Injury (DILI):	0.993
AMES Toxicity:	0.963	Rat Oral Acute Toxicity:	0.001
Maximum Recommended Daily Dose:	0.002	Skin Sensitization:	1.0
Carcinogencity:	0.001	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.0
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	1.0
Hematotoxicity:	0.096	Drug-induced Nephrotoxicity:	0.778
Genotoxicity:	0.364	RPMI-8226 Immunitoxicity:	0.225
A549 Cytotoxicity:	0.874	Hek293 Cytotoxicity:	0.241
BCF:	0.414 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.013 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.731 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.798 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	root	n.a.	n.a.	PMID[2778455]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29300477]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	fruit	n.a.	Database[Article]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23736	Myrsine africana	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC542254 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	24800
0.1-0.2	20874
0.2-0.3	3351
0.3-0.4	377
0.4-0.5	258
0.5-0.6	131
0.6-0.7	51
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.79	Intermediate Similarity	NPC480441
0.7579	Intermediate Similarity	NPC186816
0.7391	Intermediate Similarity	NPC605784
0.7212	Intermediate Similarity	NPC25523
0.7157	Intermediate Similarity	NPC14187
0.7033	Intermediate Similarity	NPC136042
0.701	Intermediate Similarity	NPC67105
0.6939	Remote Similarity	NPC203259
0.6939	Remote Similarity	NPC33054
0.6939	Remote Similarity	NPC210073
0.6939	Remote Similarity	NPC176740
0.6939	Remote Similarity	NPC471725
0.6939	Remote Similarity	NPC134532
0.6939	Remote Similarity	NPC156869
0.6939	Remote Similarity	NPC602582
0.69	Remote Similarity	NPC470443
0.6837	Remote Similarity	NPC471748
0.6774	Remote Similarity	NPC271692
0.6699	Remote Similarity	NPC473073
0.6667	Remote Similarity	NPC116458
0.6667	Remote Similarity	NPC246943
0.6636	Remote Similarity	NPC292019
0.6636	Remote Similarity	NPC202908
0.6634	Remote Similarity	NPC488073
0.6634	Remote Similarity	NPC126784
0.6634	Remote Similarity	NPC241423
0.6596	Remote Similarity	NPC84362
0.6538	Remote Similarity	NPC471669
0.6346	Remote Similarity	NPC32641
0.6346	Remote Similarity	NPC256188
0.6346	Remote Similarity	NPC35119
0.6337	Remote Similarity	NPC173582
0.6337	Remote Similarity	NPC44931
0.6337	Remote Similarity	NPC265885
0.6337	Remote Similarity	NPC181465
0.6337	Remote Similarity	NPC215710
0.6337	Remote Similarity	NPC275454
0.6337	Remote Similarity	NPC473438
0.6337	Remote Similarity	NPC227508
0.6337	Remote Similarity	NPC253788
0.6316	Remote Similarity	NPC297987
0.63	Remote Similarity	NPC251417
0.6286	Remote Similarity	NPC142142
0.6275	Remote Similarity	NPC605592
0.6238	Remote Similarity	NPC139320
0.6211	Remote Similarity	NPC249281
0.6176	Remote Similarity	NPC39834
0.6117	Remote Similarity	NPC65563
0.6117	Remote Similarity	NPC470949
0.6111	Remote Similarity	NPC470446
0.61	Remote Similarity	NPC276377
0.6091	Remote Similarity	NPC189564
0.6082	Remote Similarity	NPC46420
0.6078	Remote Similarity	NPC29958
0.6042	Remote Similarity	NPC289667
0.6019	Remote Similarity	NPC67326
0.6	Remote Similarity	NPC240306
0.6	Remote Similarity	NPC203145
0.5981	Remote Similarity	NPC486577
0.5979	Remote Similarity	NPC158674
0.5962	Remote Similarity	NPC22062
0.5962	Remote Similarity	NPC473634
0.5962	Remote Similarity	NPC138811
0.5962	Remote Similarity	NPC150164
0.5943	Remote Similarity	NPC483415
0.5926	Remote Similarity	NPC476472
0.5926	Remote Similarity	NPC294815
0.5926	Remote Similarity	NPC16194
0.5922	Remote Similarity	NPC480466
0.5905	Remote Similarity	NPC473571
0.5905	Remote Similarity	NPC110941
0.5888	Remote Similarity	NPC122467
0.5888	Remote Similarity	NPC209296
0.5888	Remote Similarity	NPC473327
0.5854	Remote Similarity	NPC223860
0.5818	Remote Similarity	NPC602448
0.5816	Remote Similarity	NPC277205
0.5816	Remote Similarity	NPC37919
0.58	Remote Similarity	NPC611303
0.5794	Remote Similarity	NPC65711
0.5728	Remote Similarity	NPC116864
0.5728	Remote Similarity	NPC244776
0.5714	Remote Similarity	NPC238376
0.5701	Remote Similarity	NPC64425
0.5701	Remote Similarity	NPC488074
0.5676	Remote Similarity	NPC135358
0.566	Remote Similarity	NPC479405
0.566	Remote Similarity	NPC303913
0.5657	Remote Similarity	NPC145038
0.5657	Remote Similarity	NPC56077
0.5657	Remote Similarity	NPC281131
0.5657	Remote Similarity	NPC253662
0.5657	Remote Similarity	NPC179950
0.5657	Remote Similarity	NPC88789
0.5657	Remote Similarity	NPC189142
0.5657	Remote Similarity	NPC77660
0.5657	Remote Similarity	NPC491374
0.5652	Remote Similarity	NPC277532
0.5644	Remote Similarity	NPC488071
0.5636	Remote Similarity	NPC89127
0.5607	Remote Similarity	NPC115674
0.5607	Remote Similarity	NPC479404
0.56	Remote Similarity	NPC27640
0.5596	Remote Similarity	NPC72016
0.5575	Remote Similarity	NPC121703
0.5556	Remote Similarity	NPC127546
0.5556	Remote Similarity	NPC57625
0.5556	Remote Similarity	NPC19709
0.5556	Remote Similarity	NPC173637
0.5556	Remote Similarity	NPC317489
0.5556	Remote Similarity	NPC223424
0.5556	Remote Similarity	NPC600591
0.5545	Remote Similarity	NPC488089
0.5545	Remote Similarity	NPC599850
0.5514	Remote Similarity	NPC155877
0.5505	Remote Similarity	NPC479403
0.5472	Remote Similarity	NPC471079
0.5462	Remote Similarity	NPC298666
0.5446	Remote Similarity	NPC470449
0.5446	Remote Similarity	NPC470445
0.5431	Remote Similarity	NPC303694
0.5429	Remote Similarity	NPC265115
0.5417	Remote Similarity	NPC156785
0.541	Remote Similarity	NPC192539
0.5392	Remote Similarity	NPC42773
0.5392	Remote Similarity	NPC59534
0.5392	Remote Similarity	NPC45522
0.5391	Remote Similarity	NPC470451
0.5385	Remote Similarity	NPC311850
0.5364	Remote Similarity	NPC12013
0.5364	Remote Similarity	NPC11432
0.5364	Remote Similarity	NPC477613
0.5357	Remote Similarity	NPC473071
0.5339	Remote Similarity	NPC488083
0.5333	Remote Similarity	NPC198199
0.5328	Remote Similarity	NPC209550
0.5328	Remote Similarity	NPC138990
0.5315	Remote Similarity	NPC229409
0.5315	Remote Similarity	NPC606657
0.531	Remote Similarity	NPC101636
0.5294	Remote Similarity	NPC305811
0.525	Remote Similarity	NPC68592
0.5246	Remote Similarity	NPC488078
0.5234	Remote Similarity	NPC8856
0.5234	Remote Similarity	NPC480463
0.5224	Remote Similarity	NPC482520
0.5224	Remote Similarity	NPC482519
0.5221	Remote Similarity	NPC483412
0.5203	Remote Similarity	NPC120952
0.5203	Remote Similarity	NPC241781
0.52	Remote Similarity	NPC67037
0.52	Remote Similarity	NPC255615
0.5196	Remote Similarity	NPC323593
0.5196	Remote Similarity	NPC203500
0.5189	Remote Similarity	NPC190003
0.5161	Remote Similarity	NPC175429
0.514	Remote Similarity	NPC254855
0.514	Remote Similarity	NPC94610
0.514	Remote Similarity	NPC95866
0.512	Remote Similarity	NPC262222
0.5116	Remote Similarity	NPC72554
0.5111	Remote Similarity	NPC482521
0.5098	Remote Similarity	NPC39360
0.5098	Remote Similarity	NPC77672
0.5098	Remote Similarity	NPC108831
0.5098	Remote Similarity	NPC133671
0.5098	Remote Similarity	NPC135391
0.5098	Remote Similarity	NPC29763
0.5098	Remote Similarity	NPC78263
0.5098	Remote Similarity	NPC210003
0.5098	Remote Similarity	NPC250069
0.5098	Remote Similarity	NPC182634
0.5091	Remote Similarity	NPC65003
0.5089	Remote Similarity	NPC483414
0.5088	Remote Similarity	NPC483413
0.5048	Remote Similarity	NPC175107
0.5046	Remote Similarity	NPC187379
0.5045	Remote Similarity	NPC204693
0.5044	Remote Similarity	NPC483416
0.5044	Remote Similarity	NPC37668
0.5044	Remote Similarity	NPC473623
0.5043	Remote Similarity	NPC292929
0.5043	Remote Similarity	NPC89052
0.5043	Remote Similarity	NPC298171
0.5043	Remote Similarity	NPC221342
0.5043	Remote Similarity	NPC476470
0.5043	Remote Similarity	NPC11468
0.5042	Remote Similarity	NPC164704
0.5041	Remote Similarity	NPC162394

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC542254 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6209
0.1-0.2	2880
0.2-0.3	52
0.3-0.4	3
0.4-0.5	2
0.5-0.6	1
0.6-0.7	2
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7917	Intermediate Similarity	NPD7251	Phase 2
0.6939	Remote Similarity	NPD6797	Phase 2
0.6604	Remote Similarity	NPD7808	Phase 3
0.5888	Remote Similarity	NPD7054	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data