NPASS Compound

Natural Product: NPC562580

Natural Product ID	NPC562580
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(3~{S},5~{R},10~{S},13~{R},14~{S},16~{S},17~{R})-14-hydroxy-3-[4-hydroxy-6-methyl-5-[(2~{S},3~{S},5~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-10,13-dimethyl-17-(5-oxo-2~{H}-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-16-yl] acetate
IUPAC Name	[(3~{S},5~{R},10~{S},13~{R},14~{S},16~{S},17~{R})-14-hydroxy-3-[4-hydroxy-6-methyl-5-[(2~{S},3~{S},5~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-10,13-dimethyl-17-(5-oxo-2~{H}-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-16-yl] acetate
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 107113 0 0 0 0 0 0 0 0999 V2000 10.2012 -2.0469 -0.6860 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4216 -0.8627 -1.1099 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9098 0.0598 -1.7839 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0845 -0.7540 -0.7520 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2960 0.3333 -1.1186 C 0 0 1 0 0 0 0 0 0 0 0 0 6.1261 -0.2147 -1.9527 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2467 -0.8135 -0.9047 C 0 0 2 0 0 0 0 0 0 0 0 0 5.6249 -2.1811 -0.8396 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7921 -0.8080 -1.2338 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2663 0.4309 -1.8620 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9546 0.9144 -1.3521 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9659 -0.1719 -1.0005 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0833 0.4828 -0.1451 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9830 -0.4245 0.5964 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3262 -0.1886 0.4152 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9758 0.1410 1.6029 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4986 1.5765 1.5557 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0077 1.6087 1.4498 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6311 1.5416 2.6837 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4820 0.4963 0.5417 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8752 0.5369 0.5509 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4058 0.8831 -0.7001 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.0554 2.0890 -0.6506 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.3676 2.0523 -0.2892 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5626 1.7683 1.1995 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.9478 1.7534 1.4574 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.2379 1.1700 -1.1346 C 0 0 1 0 0 0 0 0 0 0 0 0 -11.0535 1.9061 -1.9920 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.4418 0.2192 -1.9965 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1784 -0.9164 -2.3230 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2004 -0.2423 -1.2624 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.5867 -1.1801 -0.2764 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9692 -0.8497 0.9778 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5503 -1.6128 -0.2424 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9680 -0.7605 1.9328 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6699 -1.9000 0.3548 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8205 -2.0198 0.7034 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5651 -1.4064 -0.4617 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5971 -2.5048 -1.5401 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0113 -1.2614 -0.0189 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2084 -0.4210 1.1814 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3807 0.4983 1.0705 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5951 -0.1661 0.4229 C 0 0 1 0 0 0 0 0 0 0 0 0 6.0853 -1.1960 1.3851 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5334 0.9059 0.0461 C 0 0 1 0 0 0 0 0 0 0 0 0 7.3646 1.4967 1.0999 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2576 2.7708 1.4462 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1831 3.0889 2.4979 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3487 4.2194 3.0696 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8672 1.9584 2.7874 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4096 0.9280 1.9586 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5383 -2.8456 -0.3112 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9245 -1.7617 0.1219 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7822 -2.4881 -1.5250 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8547 1.0873 -1.7105 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6759 0.5360 -2.5915 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5945 -0.9808 -2.6311 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7315 -2.5652 -1.7458 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6386 -1.6401 -1.9887 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1578 0.3207 -2.9834 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9789 1.3044 -1.7690 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4764 1.5629 -2.1451 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0452 1.6192 -0.4733 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4463 -0.4301 -1.9718 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7279 1.1152 -0.8269 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4158 1.2525 0.5147 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7726 -0.2792 1.6982 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2279 0.1262 2.4225 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0016 2.0856 0.7141 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2353 2.1339 2.4779 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2821 2.5681 0.9657 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1032 0.9900 3.3184 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1192 0.7522 -0.4764 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5111 1.0346 -1.3758 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7672 3.1018 -0.4228 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1604 2.5979 1.8175 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0642 0.8473 1.5216 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.2786 0.8157 1.5301 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9439 0.5850 -0.4804 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8050 2.8646 -1.8659 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1153 0.6892 -2.9467 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7077 -1.3550 -3.0938 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6054 -0.8304 -1.9956 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8866 -1.8710 -0.1855 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8196 -1.3909 1.4439 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1799 -0.9341 -1.0593 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8118 -2.4146 -0.0366 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4517 -2.1053 -0.6623 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2650 -2.4818 1.0681 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8683 -2.1007 -0.6969 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0057 -1.4019 1.5939 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1289 -3.0632 0.8049 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7114 -2.0256 -2.5326 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4628 -3.1981 -1.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6961 -3.1402 -1.4925 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3600 -2.3190 0.1772 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4048 -1.0956 2.0677 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3338 0.1839 1.4759 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1734 1.4734 0.6155 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7195 0.7321 2.1237 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9048 -0.8840 2.4571 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1271 -1.5386 1.2175 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4902 -2.1575 1.3103 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9064 1.7277 -0.4119 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5830 3.5405 1.0374 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3207 0.5949 1.3783 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0636 0.1289 2.6417 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 1 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 24 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 20 33 1 0 33 34 1 0 33 35 1 0 14 36 1 0 36 37 1 0 37 38 1 0 38 39 1 6 38 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 1 43 45 1 0 45 46 1 0 46 47 2 0 47 48 1 0 48 49 2 0 48 50 1 0 50 51 1 0 45 5 1 0 51 46 1 0 43 7 1 0 40 9 1 0 38 12 1 0 35 16 1 0 31 22 1 0 1 52 1 0 1 53 1 0 1 54 1 0 5 55 1 6 6 56 1 0 6 57 1 0 8 58 1 0 9 59 1 0 10 60 1 0 10 61 1 0 11 62 1 0 11 63 1 0 12 64 1 6 13 65 1 0 13 66 1 0 14 67 1 1 16 68 1 0 17 69 1 0 17 70 1 0 18 71 1 0 19 72 1 0 20 73 1 0 22 74 1 6 24 75 1 0 25 76 1 0 25 77 1 0 26 78 1 0 27 79 1 1 28 80 1 0 29 81 1 0 30 82 1 0 31 83 1 6 32 84 1 0 33 85 1 0 34 86 1 0 34 87 1 0 34 88 1 0 36 89 1 0 36 90 1 0 37 91 1 0 37 92 1 0 39 93 1 0 39 94 1 0 39 95 1 0 40 96 1 0 41 97 1 0 41 98 1 0 42 99 1 0 42100 1 0 44101 1 0 44102 1 0 44103 1 0 45104 1 6 47105 1 0 51106 1 0 51107 1 0 M END

Standard InCHIKey	YZMYUSLXATVAEH-ODUXSGENSA-N
Standard InCHI	InChI=1S/C37H56O14/c1-17-33(51-34-32(44)31(43)30(42)26(15-38)50-34)24(40)13-28(47-17)49-21-7-9-35(3)20(12-21)5-6-23-22(35)8-10-36(4)29(19-11-27(41)46-16-19)25(48-18(2)39)14-37(23,36)45/h11,17,20-26,28-34,38,40,42-45H,5-10,12-16H2,1-4H3/t17?,20-,21+,22?,23?,24?,25+,26?,28?,29+,30-,31?,32+,33?,34+,35+,36-,37+/m1/s1
SMILES	CC(=O)O[C@H]1C[C@]2(O)C3CC[C@@H]4C[C@@H](OC5CC(O)C(O[C@@H]6OC(CO)[C@@H](O)C(O)[C@@H]6O)C(C)O5)CC[C@]4(C)C3CC[C@]2(C)[C@H]1C1=CC(=O)OC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	724.37	Volume:	703.767 ? Van der Waals volume.
Dense:	1.029	LogP:	0.852 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.554 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.054 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	39.0
TPSA:	210.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	6.0	Rings:	7.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.159	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.718	Fsp³:	0.892
MCE-18:	134.4 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.67	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.022 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.005 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.053	Promiscuous compounds:	0.12

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.239	MDCK Permeability:	-5.38
Pgp-inhibitor:	0.0	Pgp-substrate:	0.986
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):	0.055
20% Bioavailability (F20%):	0.989	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.999
Plasma Protein Binding (PPB):	61.079%	Volume Distribution (VD):	-0.364
Fu:	35.322% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.973
OATP1B3 inhibitor:	0.914	BCRP inhibitor:	0.001
BSEP inhibitor:	0.201

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.128	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.014	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.001 ? 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):

1.15

Half-life (T1/2):

2.972

ADMET: Toxicity

hERG Blockers:	0.055	hERG Blockers (10um):	0.389
Human Hepatotoxicity (H-HT):	0.624	Drug-induced Liver Injury (DILI):	0.757
AMES Toxicity:	0.869	Rat Oral Acute Toxicity:	0.844
Maximum Recommended Daily Dose:	0.989	Skin Sensitization:	1.0
Carcinogencity:	0.503	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.588
Drug-induced Neurotoxicity:	0.02	Ototoxicity:	0.966
Hematotoxicity:	0.351	Drug-induced Nephrotoxicity:	0.696
Genotoxicity:	0.941	RPMI-8226 Immunitoxicity:	0.594
A549 Cytotoxicity:	0.368	Hek293 Cytotoxicity:	0.939
BCF:	0.47 ? 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:	3.308 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.097 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.989 ? 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
NPO18864	Cryptostegia grandiflora	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18864	Cryptostegia grandiflora	Species	Apocynaceae	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 NPC562580 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	17680
0.1-0.2	26904
0.2-0.3	4467
0.3-0.4	613
0.4-0.5	96
0.5-0.6	56
0.6-0.7	30
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC475219
0.7979	Intermediate Similarity	NPC488943
0.7979	Intermediate Similarity	NPC488942
0.7789	Intermediate Similarity	NPC488938
0.7789	Intermediate Similarity	NPC488937
0.75	Intermediate Similarity	NPC488945
0.75	Intermediate Similarity	NPC488946
0.7374	Intermediate Similarity	NPC74259
0.7347	Intermediate Similarity	NPC475590
0.7263	Intermediate Similarity	NPC208193
0.7255	Intermediate Similarity	NPC488947
0.72	Intermediate Similarity	NPC120390
0.6907	Remote Similarity	NPC125077
0.6796	Remote Similarity	NPC117445
0.6796	Remote Similarity	NPC308262
0.6771	Remote Similarity	NPC236973
0.6737	Remote Similarity	NPC103534
0.6737	Remote Similarity	NPC44899
0.6737	Remote Similarity	NPC304260
0.6737	Remote Similarity	NPC29639
0.6702	Remote Similarity	NPC193893
0.6632	Remote Similarity	NPC72260
0.663	Remote Similarity	NPC5311
0.6392	Remote Similarity	NPC488935
0.6392	Remote Similarity	NPC5883
0.6392	Remote Similarity	NPC488936
0.6364	Remote Similarity	NPC475556
0.6364	Remote Similarity	NPC311706
0.6321	Remote Similarity	NPC474908
0.63	Remote Similarity	NPC231518
0.63	Remote Similarity	NPC488944
0.6275	Remote Similarity	NPC486146
0.6238	Remote Similarity	NPC486143
0.6238	Remote Similarity	NPC486142
0.6238	Remote Similarity	NPC486149
0.6162	Remote Similarity	NPC30483
0.6162	Remote Similarity	NPC470897
0.61	Remote Similarity	NPC292467
0.61	Remote Similarity	NPC40749
0.6075	Remote Similarity	NPC475419
0.6061	Remote Similarity	NPC173555
0.6	Remote Similarity	NPC474423
0.5943	Remote Similarity	NPC479360
0.5943	Remote Similarity	NPC479359
0.5941	Remote Similarity	NPC32177
0.5941	Remote Similarity	NPC469756
0.5941	Remote Similarity	NPC275901
0.5922	Remote Similarity	NPC55532
0.5895	Remote Similarity	NPC99620
0.5895	Remote Similarity	NPC471633
0.5888	Remote Similarity	NPC486144
0.5888	Remote Similarity	NPC486145
0.5888	Remote Similarity	NPC486147
0.5888	Remote Similarity	NPC486148
0.5882	Remote Similarity	NPC188234
0.5872	Remote Similarity	NPC486134
0.5872	Remote Similarity	NPC486141
0.581	Remote Similarity	NPC488939
0.5773	Remote Similarity	NPC77299
0.5773	Remote Similarity	NPC480906
0.5714	Remote Similarity	NPC119855
0.5714	Remote Similarity	NPC480914
0.5673	Remote Similarity	NPC488941
0.5673	Remote Similarity	NPC488940
0.566	Remote Similarity	NPC329986
0.566	Remote Similarity	NPC140092
0.5586	Remote Similarity	NPC329675
0.549	Remote Similarity	NPC480907
0.5472	Remote Similarity	NPC486135
0.5472	Remote Similarity	NPC486137
0.5463	Remote Similarity	NPC486138
0.5463	Remote Similarity	NPC276838
0.5429	Remote Similarity	NPC479353
0.5429	Remote Similarity	NPC240070
0.5429	Remote Similarity	NPC479354
0.5421	Remote Similarity	NPC232785
0.5421	Remote Similarity	NPC486139
0.54	Remote Similarity	NPC76572
0.54	Remote Similarity	NPC193382
0.5283	Remote Similarity	NPC480910
0.5283	Remote Similarity	NPC32793
0.5283	Remote Similarity	NPC116075
0.5283	Remote Similarity	NPC480909
0.52	Remote Similarity	NPC84987
0.5179	Remote Similarity	NPC486136
0.5149	Remote Similarity	NPC469750
0.5149	Remote Similarity	NPC99080
0.5146	Remote Similarity	NPC471353
0.514	Remote Similarity	NPC608063
0.5135	Remote Similarity	NPC479357
0.513	Remote Similarity	NPC486150
0.5098	Remote Similarity	NPC84949
0.5098	Remote Similarity	NPC480562
0.5098	Remote Similarity	NPC74945
0.5098	Remote Similarity	NPC31354
0.5098	Remote Similarity	NPC69576
0.5091	Remote Similarity	NPC146857
0.5044	Remote Similarity	NPC479358

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC562580 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6659
0.1-0.2	2395
0.2-0.3	77
0.3-0.4	8
0.4-0.5	3
0.5-0.6	3
0.6-0.7	5
0.7-0.8	0
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
0.6632	Remote Similarity	NPD8294	Phase 4
0.63	Remote Similarity	NPD8033	Approved
0.6238	Remote Similarity	NPD8377	Phase 4
0.6082	Remote Similarity	NPD8380	Approved
0.6061	Remote Similarity	NPD8296	Phase 4
0.5816	Remote Similarity	NPD8335	Phase 4
0.5714	Remote Similarity	NPD8378	Pre-clinical
0.5714	Remote Similarity	NPD8379	Approved

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