NPASS Compound

Natural Product: NPC573889

Natural Product ID	NPC573889
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})-3-[3,4-dihydroxy-6-methyl-5-[(2~{S},3~{S},5~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-14-hydroxy-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] propanoate
IUPAC Name	[(3~{S},5~{R},10~{S},13~{R},14~{S},16~{S},17~{R})-3-[3,4-dihydroxy-6-methyl-5-[(2~{S},3~{S},5~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-14-hydroxy-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] propanoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides and derivatives

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 111117 0 0 0 0 0 0 0 0999 V2000 10.5817 1.4015 3.6905 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5807 1.7596 2.6142 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6076 0.6835 2.3735 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6542 -0.3925 2.9890 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6051 0.8344 1.4518 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6658 -0.1268 1.1807 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2260 0.2838 1.4870 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6976 0.8308 0.1556 C 0 0 2 0 0 0 0 0 0 0 0 0 4.6736 2.2342 0.3542 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2994 0.4511 -0.0943 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4592 1.6625 -0.5311 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0191 1.2687 -0.7212 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9348 0.1523 -1.6792 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4912 -0.3465 -1.9214 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1058 -0.6499 -0.6180 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3512 -1.2424 -0.6645 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3905 -0.5165 -0.1972 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9385 -1.1664 0.9183 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0446 -0.5212 1.4198 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6218 0.8866 1.7494 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1709 -0.6608 0.4968 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0780 0.3667 0.4466 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3649 0.1244 0.8300 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.1633 0.3476 -0.2876 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.5071 0.1941 -0.0888 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.8151 -1.2994 -0.1409 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.2044 -1.4588 0.0588 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.0075 0.6811 1.2584 C 0 0 1 0 0 0 0 0 0 0 0 0 -11.0517 -0.3573 2.1552 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.0535 1.7396 1.7337 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4148 2.3416 2.9257 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6734 1.1549 1.9259 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.6953 2.1246 2.0163 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7334 -1.0199 -0.8827 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6057 -2.4122 -0.9679 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4316 -0.3594 -1.2839 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9992 -0.9914 -2.4432 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2098 -1.4264 0.2657 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1464 -1.7684 -0.1721 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7239 -1.0523 -1.3316 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7529 -1.9927 -2.5494 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1653 -0.6641 -1.1077 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7612 -0.1503 -2.3711 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2288 0.0531 -2.1941 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7189 0.5227 -0.8967 C 0 0 1 0 0 0 0 0 0 0 0 0 6.6124 1.7250 -1.0723 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5755 -0.5920 -0.2622 C 0 0 1 0 0 0 0 0 0 0 0 0 7.8343 -0.8661 -0.9296 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3113 -0.3780 -2.0297 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6392 -0.9374 -2.3384 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3361 -0.6323 -3.3600 O 0 0 0 0 0 0 0 0 0 0 0 0 9.9385 -1.8152 -1.3288 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8804 -1.8326 -0.4260 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1013 0.4618 3.5018 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3520 2.2092 3.7274 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1331 1.3957 4.7094 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1490 2.0596 1.7240 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0148 2.6543 3.0025 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8779 -1.0092 1.8022 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6167 -0.5982 1.7725 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1387 0.9959 2.3152 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3761 2.3869 1.3048 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8182 0.0930 0.8374 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8953 2.2208 -1.3514 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4918 2.3337 0.3813 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6076 1.1209 0.2791 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5115 2.1594 -1.2114 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2343 0.5768 -2.6881 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3576 -1.2750 -2.5083 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9976 0.4525 -2.5013 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3132 0.3535 -0.1296 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1390 0.5001 0.1483 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2741 -1.0008 2.4011 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5528 0.9380 2.0778 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1741 1.2756 2.6599 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7159 1.5905 0.9023 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7877 -1.5427 0.8652 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5844 -0.8805 1.1666 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1197 0.6303 -0.9173 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3567 -1.8044 0.7577 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4688 -1.7699 -1.0585 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.6423 -1.8891 -0.7085 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.0090 1.1429 1.0813 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8376 -0.0521 3.0711 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9580 2.5306 0.9636 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9137 3.1690 2.7100 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6871 0.5978 2.8815 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3721 2.2868 1.0841 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5376 -0.7441 -1.5958 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9951 -2.8320 -0.1616 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6538 0.6852 -1.5507 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9793 -1.9732 -2.3167 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1265 -0.8667 1.2558 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6959 -2.3913 0.6140 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1578 -2.8751 -0.4496 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8230 -1.7609 0.7268 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7224 -2.5275 -2.5530 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9844 -2.7881 -2.4585 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6885 -1.4223 -3.4950 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7266 -1.5253 -0.7409 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6226 -0.8487 -3.2497 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3111 0.8019 -2.7200 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7175 -0.9273 -2.4943 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5318 0.7318 -3.0506 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6646 1.5763 -0.7906 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2856 2.5789 -0.4153 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5922 2.1697 -2.0880 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9936 -1.5481 -0.3042 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8590 0.3467 -2.7295 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4591 -2.8627 -0.3869 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2847 -1.5063 0.5575 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 3 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 1 8 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 19 20 1 0 19 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 25 28 1 0 28 29 1 0 28 30 1 0 30 31 1 0 30 32 1 0 32 33 1 0 21 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 15 38 1 0 38 39 1 0 39 40 1 0 40 41 1 6 40 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 45 46 1 6 45 47 1 0 47 48 1 0 48 49 2 0 49 50 1 0 50 51 2 0 50 52 1 0 52 53 1 0 47 6 1 0 53 48 1 0 45 8 1 0 42 10 1 0 40 13 1 0 36 17 1 0 32 23 1 0 1 54 1 0 1 55 1 0 1 56 1 0 2 57 1 0 2 58 1 0 6 59 1 1 7 60 1 0 7 61 1 0 9 62 1 0 10 63 1 0 11 64 1 0 11 65 1 0 12 66 1 0 12 67 1 0 13 68 1 6 14 69 1 0 14 70 1 0 15 71 1 1 17 72 1 0 19 73 1 0 20 74 1 0 20 75 1 0 20 76 1 0 21 77 1 0 23 78 1 1 25 79 1 0 26 80 1 0 26 81 1 0 27 82 1 0 28 83 1 6 29 84 1 0 30 85 1 0 31 86 1 0 32 87 1 1 33 88 1 0 34 89 1 0 35 90 1 0 36 91 1 0 37 92 1 0 38 93 1 0 38 94 1 0 39 95 1 0 39 96 1 0 41 97 1 0 41 98 1 0 41 99 1 0 42100 1 0 43101 1 0 43102 1 0 44103 1 0 44104 1 0 46105 1 0 46106 1 0 46107 1 0 47108 1 1 49109 1 0 53110 1 0 53111 1 0 M END

Standard InCHIKey	XRXCJPMZYAWJHD-JJGULWAKSA-N
Standard InCHI	InChI=1S/C38H58O15/c1-5-25(40)51-23-14-38(47)22-7-6-19-13-20(8-10-36(19,3)21(22)9-11-37(38,4)27(23)18-12-26(41)48-16-18)50-34-32(46)30(44)33(17(2)49-34)53-35-31(45)29(43)28(42)24(15-39)52-35/h12,17,19-24,27-35,39,42-47H,5-11,13-16H2,1-4H3/t17?,19-,20+,21?,22?,23+,24?,27+,28-,29?,30?,31+,32?,33?,34?,35+,36+,37-,38+/m1/s1
SMILES	CCC(=O)O[C@H]1C[C@]2(O)C3CC[C@@H]4C[C@@H](OC5OC(C)C(O[C@@H]6OC(CO)[C@@H](O)C(O)[C@@H]6O)C(O)C5O)CC[C@]4(C)C3CC[C@]2(C)[C@H]1C1=CC(=O)OC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	754.38	Volume:	729.853 ? Van der Waals volume.
Dense:	1.034	LogP:	0.582 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.354 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.011 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	39.0
TPSA:	231.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	7.0	Rings:	7.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.13	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.777	Fsp³:	0.895
MCE-18:	136.111 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.561	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:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.065	Promiscuous compounds:	0.064

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.372	MDCK Permeability:	-5.248
Pgp-inhibitor:	0.0	Pgp-substrate:	0.998
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):	0.194
20% Bioavailability (F20%):	0.998	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.999
Plasma Protein Binding (PPB):	60.023%	Volume Distribution (VD):	-0.467
Fu:	38.051% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.35
OATP1B3 inhibitor:	0.431	BCRP inhibitor:	0.001
BSEP inhibitor:	0.411

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.322	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.026	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.787	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.062
HLM stability:	0.015 ? 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):

1.097

Half-life (T1/2):

2.848

ADMET: Toxicity

hERG Blockers:	0.04	hERG Blockers (10um):	0.366
Human Hepatotoxicity (H-HT):	0.582	Drug-induced Liver Injury (DILI):	0.652
AMES Toxicity:	0.844	Rat Oral Acute Toxicity:	0.765
Maximum Recommended Daily Dose:	0.98	Skin Sensitization:	1.0
Carcinogencity:	0.466	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.457
Drug-induced Neurotoxicity:	0.024	Ototoxicity:	0.971
Hematotoxicity:	0.366	Drug-induced Nephrotoxicity:	0.587
Genotoxicity:	0.925	RPMI-8226 Immunitoxicity:	0.576
A549 Cytotoxicity:	0.264	Hek293 Cytotoxicity:	0.924
BCF:	0.481 ? 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:	3.383 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.238 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.071 ? 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 NPC573889 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	17610
0.1-0.2	26896
0.2-0.3	4312
0.3-0.4	819
0.4-0.5	108
0.5-0.6	56
0.6-0.7	39
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8352	Intermediate Similarity	NPC475219
0.8065	Intermediate Similarity	NPC488943
0.8065	Intermediate Similarity	NPC488942
0.7778	Intermediate Similarity	NPC236973
0.7576	Intermediate Similarity	NPC488945
0.7576	Intermediate Similarity	NPC488946
0.75	Intermediate Similarity	NPC488938
0.75	Intermediate Similarity	NPC488937
0.7021	Intermediate Similarity	NPC40749
0.699	Remote Similarity	NPC488947
0.6889	Remote Similarity	NPC5311
0.6842	Remote Similarity	NPC32177
0.6842	Remote Similarity	NPC469756
0.6842	Remote Similarity	NPC275901
0.6771	Remote Similarity	NPC188234
0.6701	Remote Similarity	NPC231518
0.6701	Remote Similarity	NPC488944
0.6633	Remote Similarity	NPC486143
0.6633	Remote Similarity	NPC486142
0.6633	Remote Similarity	NPC486149
0.6465	Remote Similarity	NPC208193
0.6458	Remote Similarity	NPC5883
0.6442	Remote Similarity	NPC120390
0.6408	Remote Similarity	NPC475590
0.6392	Remote Similarity	NPC30483
0.6392	Remote Similarity	NPC470897
0.6311	Remote Similarity	NPC479360
0.6311	Remote Similarity	NPC479359
0.6304	Remote Similarity	NPC99620
0.6289	Remote Similarity	NPC103534
0.6289	Remote Similarity	NPC44899
0.6289	Remote Similarity	NPC304260
0.6289	Remote Similarity	NPC29639
0.6286	Remote Similarity	NPC74259
0.625	Remote Similarity	NPC486144
0.625	Remote Similarity	NPC486145
0.625	Remote Similarity	NPC486147
0.625	Remote Similarity	NPC486148
0.6176	Remote Similarity	NPC486146
0.6162	Remote Similarity	NPC292467
0.6122	Remote Similarity	NPC488935
0.6122	Remote Similarity	NPC488936
0.61	Remote Similarity	NPC32793
0.61	Remote Similarity	NPC116075
0.604	Remote Similarity	NPC488941
0.604	Remote Similarity	NPC488940
0.6	Remote Similarity	NPC77299
0.6	Remote Similarity	NPC480906
0.598	Remote Similarity	NPC125077
0.5938	Remote Similarity	NPC480914
0.5926	Remote Similarity	NPC117445
0.5926	Remote Similarity	NPC474908
0.5926	Remote Similarity	NPC308262
0.5909	Remote Similarity	NPC474423
0.5859	Remote Similarity	NPC480907
0.5833	Remote Similarity	NPC475419
0.5825	Remote Similarity	NPC486135
0.5825	Remote Similarity	NPC486137
0.5784	Remote Similarity	NPC479353
0.5784	Remote Similarity	NPC240070
0.5784	Remote Similarity	NPC479354
0.578	Remote Similarity	NPC486134
0.578	Remote Similarity	NPC486141
0.5773	Remote Similarity	NPC76572
0.5773	Remote Similarity	NPC193382
0.5769	Remote Similarity	NPC232785
0.5769	Remote Similarity	NPC486139
0.5728	Remote Similarity	NPC264336
0.5714	Remote Similarity	NPC488939
0.56	Remote Similarity	NPC193893
0.5545	Remote Similarity	NPC72260
0.5524	Remote Similarity	NPC59288
0.551	Remote Similarity	NPC469750
0.5505	Remote Similarity	NPC486136
0.55	Remote Similarity	NPC471353
0.5481	Remote Similarity	NPC475556
0.5481	Remote Similarity	NPC480910
0.5481	Remote Similarity	NPC480909
0.5481	Remote Similarity	NPC311706
0.5463	Remote Similarity	NPC479357
0.5435	Remote Similarity	NPC119855
0.5421	Remote Similarity	NPC329986
0.5421	Remote Similarity	NPC140092
0.5408	Remote Similarity	NPC84987
0.537	Remote Similarity	NPC486138
0.537	Remote Similarity	NPC276838
0.5306	Remote Similarity	NPC471633
0.5283	Remote Similarity	NPC475629
0.5253	Remote Similarity	NPC196429
0.5234	Remote Similarity	NPC55532
0.52	Remote Similarity	NPC479356
0.52	Remote Similarity	NPC479355
0.5196	Remote Similarity	NPC179412
0.5196	Remote Similarity	NPC471356
0.5192	Remote Similarity	NPC173555
0.5149	Remote Similarity	NPC199428
0.5149	Remote Similarity	NPC109448
0.5149	Remote Similarity	NPC310341
0.505	Remote Similarity	NPC157376
0.505	Remote Similarity	NPC99080
0.505	Remote Similarity	NPC142066
0.505	Remote Similarity	NPC603972
0.5047	Remote Similarity	NPC486130
0.5043	Remote Similarity	NPC486150

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC573889 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6652
0.1-0.2	2395
0.2-0.3	82
0.3-0.4	6
0.4-0.5	9
0.5-0.6	5
0.6-0.7	1
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
0.6701	Remote Similarity	NPD8033	Approved
0.5545	Remote Similarity	NPD8294	Phase 4
0.5234	Remote Similarity	NPD8377	Phase 4
0.5196	Remote Similarity	NPD8380	Approved
0.5192	Remote Similarity	NPD8296	Phase 4
0.5098	Remote Similarity	NPD8335	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