NPASS Compound

Natural Product: NPC600057

Natural Product ID	NPC600057
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LPGWZGMPDKDHEP-HLTPFJCJSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL508191
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 115124 0 0 0 0 0 0 0 0999 V2000 -6.8888 -1.3221 -1.0646 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7706 -0.8953 0.0875 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0185 -0.0052 1.0496 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.4871 1.2528 0.4764 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5304 2.0256 1.1370 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.5393 2.6812 0.4023 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1822 2.1307 0.2251 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0686 0.9469 -0.6556 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8478 -0.3436 -0.3753 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8303 -0.9993 -1.5612 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.0331 -0.1796 -2.5993 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1021 -0.3720 -3.9755 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3260 0.6630 -4.8486 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4819 1.9134 -4.3101 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4121 2.0948 -2.9460 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1864 1.0549 -2.0542 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6751 -1.0683 0.8994 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8795 -2.5114 0.8367 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7659 -3.1479 1.4966 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1121 -3.3701 0.0337 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3294 -4.7649 -0.0081 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2138 -0.8945 1.2679 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3659 -0.1684 0.4673 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9785 0.0162 0.7763 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4812 -0.5366 1.9084 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6678 -1.2727 2.7401 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6821 -1.4478 2.4118 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5223 -2.1845 3.2297 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9763 -2.7522 4.4038 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9032 -0.1814 2.0080 N 0 0 0 0 0 0 0 0 0 0 0 0 3.7614 -0.9902 2.8431 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0591 0.9797 1.2036 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3711 1.3229 0.6202 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1137 2.1333 -0.5324 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3075 2.0474 1.4446 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7978 1.6913 2.5470 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7563 3.3185 0.9970 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6754 4.0798 1.7602 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9217 0.0370 -0.0207 C 0 0 2 0 0 0 0 0 0 0 0 0 6.2718 0.2699 -0.3851 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2434 -0.4602 0.3279 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6885 -0.2798 0.0130 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9195 -1.2697 1.2340 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0678 -0.2360 -1.2076 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3074 -1.6989 -1.6258 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6983 -2.0129 -2.0281 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6674 0.5643 -2.3318 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9571 0.8329 -3.3821 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5518 0.3351 -3.4424 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8893 0.4275 -2.1894 N 0 0 0 0 0 0 0 0 0 0 0 0 1.5376 1.7988 -1.9384 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5123 2.0193 -0.4711 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0745 0.7280 0.0814 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6058 -0.0640 -1.0424 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4696 -0.5159 2.0458 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7937 -0.0549 1.7201 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0611 1.3334 2.3007 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0747 -0.7613 1.9468 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.2004 -0.0805 2.3973 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4096 -2.1728 -1.5606 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7353 -0.5455 -1.8157 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9238 -1.7599 -0.6812 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1202 -1.8299 0.5758 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6655 -0.4152 -0.3431 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3857 1.9163 0.2808 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1231 1.0323 -0.5712 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5174 3.7565 0.7772 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9572 2.8383 -0.6468 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5869 2.0171 1.1521 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5972 2.9565 -0.2945 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6792 -2.0492 -1.7460 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9723 -1.3751 -4.3437 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3806 0.5125 -5.9319 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6602 2.7750 -4.9265 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5358 3.0917 -2.5423 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2148 -5.0112 -0.6221 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4436 -5.2795 -0.3829 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5255 -5.1241 1.0439 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7133 0.2838 -0.4300 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0623 -1.7142 3.6409 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6944 -3.4164 4.9147 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5567 -1.9713 5.0747 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0931 -3.4023 4.1334 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7438 -0.6268 3.0574 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2355 -1.1051 3.8514 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8103 -2.0395 2.4204 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6132 1.8791 1.7541 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4252 3.0473 -0.3941 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3778 3.3794 2.2425 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0500 4.6069 2.5365 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1723 4.8141 1.1045 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8170 -0.7525 0.7232 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1662 0.1837 0.8945 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1173 -1.2845 -0.1300 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7790 0.3725 -0.8795 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5451 -2.0182 -2.3962 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0424 -2.3660 -0.7487 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2089 -2.5715 -1.2202 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2480 -1.0912 -2.2541 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7393 -2.7221 -2.9069 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6871 0.9098 -2.2607 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3716 1.4163 -4.2225 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0149 1.0652 -4.1262 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4497 -0.6293 -3.9779 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5026 1.9978 -2.3469 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1831 2.5352 -2.4393 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4453 2.1270 -0.1010 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0099 2.9261 -0.1199 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1793 -1.1211 -0.9123 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8835 0.2211 2.6139 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6068 -1.3496 2.8168 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8166 -0.0347 0.5633 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8887 1.3432 3.0375 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2032 1.7653 2.7965 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0667 -1.8480 1.9246 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 6 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 9 17 1 0 17 18 1 6 18 19 2 0 18 20 1 0 20 21 1 0 17 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 1 0 25 30 1 0 30 31 1 0 30 32 1 0 32 33 1 0 33 34 1 6 33 35 1 0 35 36 2 0 35 37 1 0 37 38 1 0 33 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 41 43 2 0 39 44 1 0 44 45 1 6 45 46 1 0 44 47 1 0 47 48 2 0 48 49 1 0 49 50 1 0 50 51 1 0 51 52 1 0 53 52 1 6 53 54 1 0 17 55 1 0 55 56 1 0 56 57 1 0 56 58 1 0 58 59 1 0 58 3 1 0 59 3 1 0 57 5 1 0 16 8 1 0 27 22 1 0 53 32 1 0 16 11 1 0 53 24 1 0 54 44 1 0 54 50 1 0 1 60 1 0 1 61 1 0 1 62 1 0 2 63 1 0 2 64 1 0 4 65 1 0 4 66 1 0 6 67 1 0 6 68 1 0 7 69 1 0 7 70 1 0 10 71 1 0 12 72 1 0 13 73 1 0 14 74 1 0 15 75 1 0 21 76 1 0 21 77 1 0 21 78 1 0 23 79 1 0 26 80 1 0 29 81 1 0 29 82 1 0 29 83 1 0 31 84 1 0 31 85 1 0 31 86 1 0 32 87 1 1 34 88 1 0 38 89 1 0 38 90 1 0 38 91 1 0 39 92 1 1 42 93 1 0 42 94 1 0 42 95 1 0 45 96 1 0 45 97 1 0 46 98 1 0 46 99 1 0 46100 1 0 47101 1 0 48102 1 0 49103 1 0 49104 1 0 51105 1 0 51106 1 0 52107 1 0 52108 1 0 54109 1 1 55110 1 0 55111 1 0 56112 1 6 57113 1 0 57114 1 0 58115 1 6 M END

Standard InCHIKey	LPGWZGMPDKDHEP-HLTPFJCJSA-N
Standard InCHI	InChI=1S/C46H56N4O9/c1-8-42-16-12-18-50-20-17-44(37(42)50)30-21-31(34(55-5)22-33(30)48(4)38(44)46(54,41(53)57-7)39(42)58-26(3)51)45(40(52)56-6)23-27-24-49(25-43(9-2)36(27)59-43)19-15-29-28-13-10-11-14-32(28)47-35(29)45/h10-14,16,21-22,27,36-39,47,54H,8-9,15,17-20,23-25H2,1-7H3/t27-,36-,37+,38-,39-,42-,43+,44-,45+,46+/m1/s1
SMILES	CC[C@]12CN3CCc4c([nH]c5ccccc45)[C@@](C(=O)OC)(c4cc5c(cc4OC)N(C)[C@H]4[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]6(CC)C=CCN7CC[C@]54[C@@H]76)C[C@H](C3)[C@H]1O2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	808.4	Volume:	812.705 ? Van der Waals volume.
Dense:	0.995	LogP:	3.198 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.898 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.283 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	50.0
TPSA:	146.4 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	2.0	Rings:	10.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.154	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.301	Fsp³:	0.587
MCE-18:	287.562 ? 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:	0.436	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.877 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.584 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.985

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.966	MDCK Permeability:	-5.165
Pgp-inhibitor:	0.0	Pgp-substrate:	1.0
PAMPA:	0.023 ? 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):	0.0
20% Bioavailability (F20%):	0.048	30% Bioavailability (F30%):	0.974
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.133	MRP1:	1.0
Plasma Protein Binding (PPB):	88.244%	Volume Distribution (VD):	0.55
Fu:	12.478% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.942
OATP1B3 inhibitor:	0.979	BCRP inhibitor:	0.728
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.065
CYP2D6-inhibitor:	0.481	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.564
CYP2B6-substrate:	0.011	CYP2C8-inhibitor:	0.054
HLM stability:	0.998 ? 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):

9.4

Half-life (T1/2):

1.57

ADMET: Toxicity

hERG Blockers:	0.816	hERG Blockers (10um):	0.517
Human Hepatotoxicity (H-HT):	0.87	Drug-induced Liver Injury (DILI):	0.887
AMES Toxicity:	0.8	Rat Oral Acute Toxicity:	0.94
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	0.998
Carcinogencity:	0.208	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.998
Drug-induced Neurotoxicity:	0.942	Ototoxicity:	0.88
Hematotoxicity:	0.864	Drug-induced Nephrotoxicity:	0.999
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.618
A549 Cytotoxicity:	0.948	Hek293 Cytotoxicity:	0.957
BCF:	0.976 ? 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:	4.283 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.701 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.354 ? 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
NPO62806	Catharanthus roseus (L.) G. Don	Genus	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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

Activity Type	# Activity
ED50	4

Activity Type	# Activity
Cell line	3
Non-molecular	1

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
NPT91	Cell line	KB	Homo sapiens	ED50	=	1.0	10'-3 ug/ml	PMID[9461649]
NPT168	Cell line	P388	Mus musculus	ED50	=	1.7	ug ml-1	PMID[7264682]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	2.4	ug ml-1	PMID[7264682]
NPT30043	Cell line	Vero	Chlorocebus sabaeus	ED50	>	1.0	ug ml-1	PMID[9461649]

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 NPC600057 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	18943
0.1-0.2	30243
0.2-0.3	618
0.3-0.4	44
0.4-0.5	0
0.5-0.6	3
0.6-0.7	1
0.7-0.8	2
0.8-0.85	3
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	NPC277353
0.8189	Intermediate Similarity	NPC195788
0.8189	Intermediate Similarity	NPC237901
0.8189	Intermediate Similarity	NPC608514
0.7939	Intermediate Similarity	NPC485509
0.6912	Remote Similarity	NPC302688
0.5878	Remote Similarity	NPC260909
0.5743	Remote Similarity	NPC481036
0.5724	Remote Similarity	NPC489610

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC600057 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4270
0.1-0.2	4827
0.2-0.3	36
0.3-0.4	3
0.4-0.5	0
0.5-0.6	2
0.6-0.7	8
0.7-0.8	2
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8189	Intermediate Similarity	NPD8466	Phase 4
0.8189	Intermediate Similarity	NPD8467	Approved
0.7939	Intermediate Similarity	NPD8465	Approved
0.7239	Intermediate Similarity	NPD8489	Phase 1
0.6912	Remote Similarity	NPD8428	Approved
0.6912	Remote Similarity	NPD8429	Phase 4
0.6861	Remote Similarity	NPD8425	Approved
0.6861	Remote Similarity	NPD8426	Phase 4
0.6713	Remote Similarity	NPD8427	Approved
0.6619	Remote Similarity	NPD8364	Approved
0.6479	Remote Similarity	NPD8363	Approved
0.6479	Remote Similarity	NPD8365	Clinical (unspecified phase)
0.5878	Remote Similarity	NPD8460	Phase 4
0.5724	Remote Similarity	NPD8459	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