NPASS Compound

Natural Product: NPC304259

Natural Product ID	NPC304259
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BPGWSHOXZQEBEG-AJVGRJBPSA-N
IUPAC Name	n.a.
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 104110 0 0 0 0 0 0 0 0999 V2000 -4.8805 2.6781 0.1127 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2456 1.3024 0.0194 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2019 0.2357 0.5156 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.5010 -1.0950 0.3325 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1483 -0.9888 1.0025 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3489 0.1421 0.4448 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0423 1.3190 0.7312 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1097 0.1498 1.0404 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0615 0.0613 0.0937 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7866 1.2688 0.2927 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1811 1.1717 -0.2237 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7918 -0.1226 0.3336 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7020 -0.0364 1.8309 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0118 -1.2463 -0.2578 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6913 -2.5647 -0.1138 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0346 -2.4606 -0.8471 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8623 -1.4736 -0.0865 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2505 -0.1103 -0.0509 C 0 0 2 0 0 0 0 0 0 0 0 0 5.0290 0.7231 0.9499 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4324 0.8726 0.4111 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1048 -0.4346 0.1594 C 0 0 2 0 0 0 0 0 0 0 0 0 7.6095 -1.1108 1.3912 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2596 -0.1814 -0.8079 C 0 0 1 0 0 0 0 0 0 0 0 0 7.5272 -0.0007 -2.1028 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3382 -0.9523 -2.0542 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2523 -1.4028 -0.6253 C 0 0 2 0 0 0 0 0 0 0 0 0 6.8746 -2.6526 -0.5396 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0605 1.0030 -0.4196 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1911 2.1612 -1.0661 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0683 3.0523 -0.3416 C 0 0 0 0 0 0 0 0 0 0 0 0 10.4184 4.2385 -0.6636 O 0 0 0 0 0 0 0 0 0 0 0 0 10.4823 2.3921 0.7954 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8872 1.1106 0.7898 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6247 -1.2463 0.3364 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1533 -2.1499 0.9544 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4597 -3.1062 -0.0106 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3561 0.3333 -0.2228 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5100 0.6272 0.5055 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.4841 -0.5007 0.5312 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.8071 0.0832 0.9844 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.2168 1.0373 -0.1216 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.1483 2.0280 -0.4427 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.9877 2.0956 -1.9456 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4345 0.9130 -2.4270 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9454 1.8402 0.1219 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.3934 1.6588 0.2906 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.7729 -0.8793 1.1454 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1048 -1.4392 1.4900 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5092 2.7012 1.0141 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1126 3.4804 0.1044 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5371 2.7930 -0.7673 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0613 1.0954 -1.0610 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3244 0.3987 1.5960 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3920 -1.2749 -0.7467 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5638 -1.9273 0.9105 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3646 -0.7796 2.0889 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2493 0.0621 -0.6543 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5597 0.0127 -0.9036 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7513 1.6017 1.3697 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2933 2.1222 -0.2602 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7445 2.0537 0.1430 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1664 1.0670 -1.3092 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6775 -0.0266 2.2247 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1657 0.9239 2.1437 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2476 -0.8558 2.3411 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8912 -1.0428 -1.3441 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0856 -3.3811 -0.5289 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9552 -2.7276 0.9615 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8076 -2.0257 -1.8406 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5478 -3.4194 -0.8871 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9361 -1.8327 0.9677 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3404 0.4350 -1.0261 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5961 1.7595 0.9583 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0854 0.2663 1.9412 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4390 1.5429 -0.4494 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0045 1.4017 1.2232 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7181 -1.2866 1.3686 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1529 -2.1133 1.5040 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3662 -0.4895 2.2801 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9025 -1.0973 -0.8876 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1910 -0.2359 -2.9865 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1391 1.0008 -2.2838 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4252 -0.5215 -2.4610 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6030 -1.8127 -2.7365 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3745 -3.2955 0.0170 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7170 2.4133 -1.9972 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3098 1.0334 1.7425 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7364 0.3849 0.7776 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6156 -1.5606 1.4062 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0500 -2.0370 -0.2028 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9843 -3.9516 0.4937 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1266 -2.7058 -0.7988 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5179 -3.5026 -0.4393 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1408 0.7159 1.5749 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6764 -0.9719 -0.4543 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6273 0.6773 1.9228 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4707 0.4120 -1.0009 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5333 3.0450 -0.1412 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2533 2.9059 -2.2284 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9357 2.3515 -2.4579 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0989 0.2025 -2.5023 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.1867 1.3444 -0.2117 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6014 -1.3365 2.0169 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3679 -2.3360 1.1542 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 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 1 12 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 20 21 1 0 21 22 1 1 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 6 23 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 14 34 1 0 4 35 1 0 35 36 1 0 3 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 42 45 1 0 41 46 1 0 40 47 1 0 39 48 1 0 7 2 1 0 34 9 1 0 45 38 1 0 18 12 1 0 26 21 1 0 33 28 1 0 26 17 1 0 1 49 1 0 1 50 1 0 1 51 1 0 2 52 1 6 3 53 1 1 4 54 1 6 5 55 1 0 5 56 1 0 6 57 1 6 9 58 1 6 10 59 1 0 10 60 1 0 11 61 1 0 11 62 1 0 13 63 1 0 13 64 1 0 13 65 1 0 14 66 1 6 15 67 1 0 15 68 1 0 16 69 1 0 16 70 1 0 17 71 1 1 18 72 1 6 19 73 1 0 19 74 1 0 20 75 1 0 20 76 1 0 22 77 1 0 22 78 1 0 22 79 1 0 23 80 1 6 24 81 1 0 24 82 1 0 25 83 1 0 25 84 1 0 27 85 1 0 29 86 1 0 33 87 1 0 33 88 1 0 34 89 1 0 34 90 1 0 36 91 1 0 36 92 1 0 36 93 1 0 38 94 1 1 39 95 1 6 40 96 1 1 41 97 1 6 42 98 1 1 43 99 1 0 43100 1 0 44101 1 0 46102 1 0 47103 1 0 48104 1 0 M END

Standard InCHIKey	BPGWSHOXZQEBEG-AJVGRJBPSA-N
Standard InCHI	InChI=1S/C36H56O12/c1-18-32(48-33-31(41)30(40)29(39)26(16-37)47-33)25(43-4)15-28(45-18)46-21-7-10-34(2)20(14-21)5-6-24-23(34)8-11-35(3)22(9-12-36(24,35)42)19-13-27(38)44-17-19/h13,18,20-26,28-33,37,39-42H,5-12,14-17H2,1-4H3/t18-,20+,21+,22+,23+,24-,25-,26+,28+,29+,30-,31+,32-,33-,34+,35-,36+/m1/s1
SMILES	C[C@@H]1[C@H]([C@@H](C[C@@H](O1)O[C@H]1CC[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](CC[C@]32O)C2=CC(=O)OC2)C1)OC)O[C@@H]1[C@H]([C@@H]([C@H]([C@H](CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	680.38	Volume:	671.527 ? Van der Waals volume.
Dense:	1.013	LogP:	1.461 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.294 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.313 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	38.0
TPSA:	173.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	5.0	Rings:	7.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.196	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.537	Fsp³:	0.917
MCE-18:	129.333 ? 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:	0.834	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.172	Promiscuous compounds:	0.285

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.157	MDCK Permeability:	-5.197
Pgp-inhibitor:	0.126	Pgp-substrate:	0.575
PAMPA:	0.754 ? 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):	0.127
20% Bioavailability (F20%):	0.739	30% Bioavailability (F30%):	0.986
50% Bioavailability (F50%):	0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.04	MRP1:	0.526
Plasma Protein Binding (PPB):	77.757%	Volume Distribution (VD):	-0.272
Fu:	19.53% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.988	BCRP inhibitor:	0.003
BSEP inhibitor:	0.924

ADMET: Metabolism

CYP1A2-inhibitor:	0.541	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.5	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.908	CYP3A4-substrate:	0.984
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.076
HLM stability:	0.077 ? 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):

1.606

Half-life (T1/2):

2.824

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.228
Human Hepatotoxicity (H-HT):	0.635	Drug-induced Liver Injury (DILI):	0.985
AMES Toxicity:	0.978	Rat Oral Acute Toxicity:	0.294
Maximum Recommended Daily Dose:	0.743	Skin Sensitization:	1.0
Carcinogencity:	0.805	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.064
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.977
Hematotoxicity:	0.692	Drug-induced Nephrotoxicity:	0.998
Genotoxicity:	0.817	RPMI-8226 Immunitoxicity:	0.517
A549 Cytotoxicity:	0.884	Hek293 Cytotoxicity:	0.812
BCF:	0.886 ? 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:	3.541 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.258 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.416 ? 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
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12987	Rhododendron farrerae	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14048	Cryptotaenia japonica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14048	Cryptotaenia japonica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14048	Cryptotaenia japonica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14048	Cryptotaenia japonica	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12987	Rhododendron farrerae	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18054	Curvularia coicis	Species	Pleosporaceae	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 NPC304259 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	14196
0.1-0.2	29943
0.2-0.3	4691
0.3-0.4	773
0.4-0.5	95
0.5-0.6	63
0.6-0.7	49
0.7-0.8	1
0.8-0.85	4
0.85-0.9	7
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9205	High Similarity	NPC475419
0.8804	High Similarity	NPC474423
0.8736	High Similarity	NPC329986
0.8736	High Similarity	NPC140092
0.8571	High Similarity	NPC74259
0.8506	High Similarity	NPC486143
0.8506	High Similarity	NPC486142
0.8506	High Similarity	NPC486149
0.8478	Intermediate Similarity	NPC474908
0.837	Intermediate Similarity	NPC120390
0.8293	Intermediate Similarity	NPC5311
0.8111	Intermediate Similarity	NPC486146
0.7957	Intermediate Similarity	NPC486144
0.7957	Intermediate Similarity	NPC486145
0.7957	Intermediate Similarity	NPC486147
0.7957	Intermediate Similarity	NPC486148
0.7753	Intermediate Similarity	NPC236973
0.7717	Intermediate Similarity	NPC146857
0.764	Intermediate Similarity	NPC30483
0.764	Intermediate Similarity	NPC470897
0.7579	Intermediate Similarity	NPC475590
0.7556	Intermediate Similarity	NPC292467
0.7526	Intermediate Similarity	NPC486134
0.7526	Intermediate Similarity	NPC486141
0.75	Intermediate Similarity	NPC486135
0.75	Intermediate Similarity	NPC486137
0.7419	Intermediate Similarity	NPC232785
0.7419	Intermediate Similarity	NPC486139
0.7412	Intermediate Similarity	NPC99620
0.7347	Intermediate Similarity	NPC117445
0.7347	Intermediate Similarity	NPC308262
0.7241	Intermediate Similarity	NPC77299
0.7241	Intermediate Similarity	NPC480906
0.7204	Intermediate Similarity	NPC231518
0.7204	Intermediate Similarity	NPC488944
0.7172	Intermediate Similarity	NPC329675
0.7172	Intermediate Similarity	NPC194716
0.7159	Intermediate Similarity	NPC84949
0.7159	Intermediate Similarity	NPC480562
0.7159	Intermediate Similarity	NPC74945
0.7159	Intermediate Similarity	NPC31354
0.7159	Intermediate Similarity	NPC69576
0.7159	Intermediate Similarity	NPC480914
0.7128	Intermediate Similarity	NPC125077
0.7083	Intermediate Similarity	NPC486138
0.7083	Intermediate Similarity	NPC276838
0.7041	Intermediate Similarity	NPC486136
0.6947	Remote Similarity	NPC208193
0.6931	Remote Similarity	NPC329784
0.6915	Remote Similarity	NPC240070
0.6848	Remote Similarity	NPC72260
0.6848	Remote Similarity	NPC480907
0.6818	Remote Similarity	NPC471633
0.6809	Remote Similarity	NPC32177
0.6809	Remote Similarity	NPC469756
0.6809	Remote Similarity	NPC275901
0.6778	Remote Similarity	NPC76572
0.6778	Remote Similarity	NPC193382
0.6768	Remote Similarity	NPC479360
0.6768	Remote Similarity	NPC479359
0.6768	Remote Similarity	NPC488943
0.6768	Remote Similarity	NPC488942
0.6737	Remote Similarity	NPC188234
0.6737	Remote Similarity	NPC480910
0.6737	Remote Similarity	NPC480909
0.6667	Remote Similarity	NPC475629
0.663	Remote Similarity	NPC484202
0.6602	Remote Similarity	NPC486150
0.66	Remote Similarity	NPC488938
0.66	Remote Similarity	NPC488937
0.6598	Remote Similarity	NPC55532
0.6593	Remote Similarity	NPC199428
0.6593	Remote Similarity	NPC109448
0.6593	Remote Similarity	NPC310341
0.6562	Remote Similarity	NPC479353
0.6562	Remote Similarity	NPC479354
0.6562	Remote Similarity	NPC486130
0.65	Remote Similarity	NPC475219
0.6495	Remote Similarity	NPC488941
0.6495	Remote Similarity	NPC488940
0.6495	Remote Similarity	NPC486127
0.6484	Remote Similarity	NPC469750
0.6452	Remote Similarity	NPC483822
0.6392	Remote Similarity	NPC475556
0.6392	Remote Similarity	NPC311706
0.6381	Remote Similarity	NPC488945
0.6381	Remote Similarity	NPC488946
0.6374	Remote Similarity	NPC84987
0.6277	Remote Similarity	NPC93883
0.6176	Remote Similarity	NPC479357
0.6176	Remote Similarity	NPC486132
0.6176	Remote Similarity	NPC486131
0.6168	Remote Similarity	NPC488947
0.6139	Remote Similarity	NPC488939
0.6117	Remote Similarity	NPC486128
0.6022	Remote Similarity	NPC196429
0.598	Remote Similarity	NPC247190
0.596	Remote Similarity	NPC40749
0.5957	Remote Similarity	NPC99080
0.5938	Remote Similarity	NPC471353
0.5938	Remote Similarity	NPC305574
0.59	Remote Similarity	NPC32793
0.59	Remote Similarity	NPC116075
0.5888	Remote Similarity	NPC486140
0.5833	Remote Similarity	NPC486133
0.5789	Remote Similarity	NPC157376
0.5789	Remote Similarity	NPC142066
0.5789	Remote Similarity	NPC480915
0.5789	Remote Similarity	NPC603972
0.5766	Remote Similarity	NPC286809
0.5758	Remote Similarity	NPC173555
0.5755	Remote Similarity	NPC329636
0.5755	Remote Similarity	NPC479358
0.5745	Remote Similarity	NPC99728
0.5745	Remote Similarity	NPC87250
0.5745	Remote Similarity	NPC244402
0.5745	Remote Similarity	NPC50305
0.5728	Remote Similarity	NPC469749
0.5714	Remote Similarity	NPC193893
0.567	Remote Similarity	NPC250556
0.5625	Remote Similarity	NPC17896
0.5625	Remote Similarity	NPC469755
0.5625	Remote Similarity	NPC284406
0.5625	Remote Similarity	NPC197707
0.5625	Remote Similarity	NPC251866
0.5612	Remote Similarity	NPC179412
0.5612	Remote Similarity	NPC471356
0.56	Remote Similarity	NPC103534
0.56	Remote Similarity	NPC44899
0.56	Remote Similarity	NPC304260
0.56	Remote Similarity	NPC29639
0.5575	Remote Similarity	NPC486152
0.5566	Remote Similarity	NPC476221
0.5566	Remote Similarity	NPC477709
0.5534	Remote Similarity	NPC610296
0.5464	Remote Similarity	NPC479356
0.5464	Remote Similarity	NPC34390
0.5464	Remote Similarity	NPC479355
0.5417	Remote Similarity	NPC473852
0.5408	Remote Similarity	NPC243196
0.5408	Remote Similarity	NPC152615
0.5385	Remote Similarity	NPC264336
0.5354	Remote Similarity	NPC146456
0.5354	Remote Similarity	NPC180079
0.5306	Remote Similarity	NPC477580
0.5227	Remote Similarity	NPC268829
0.5227	Remote Similarity	NPC295110
0.5189	Remote Similarity	NPC59288
0.5155	Remote Similarity	NPC158344
0.5155	Remote Similarity	NPC474418
0.5146	Remote Similarity	NPC5883
0.5143	Remote Similarity	NPC608063
0.5051	Remote Similarity	NPC219085
0.5051	Remote Similarity	NPC309034
0.505	Remote Similarity	NPC77319
0.505	Remote Similarity	NPC471351
0.505	Remote Similarity	NPC471355
0.5048	Remote Similarity	NPC27363
0.5046	Remote Similarity	NPC477492

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC304259 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5899
0.1-0.2	3125
0.2-0.3	106
0.3-0.4	4
0.4-0.5	6
0.5-0.6	6
0.6-0.7	3
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
0.7204	Intermediate Similarity	NPD8033	Approved
0.6848	Remote Similarity	NPD8294	Phase 4
0.6598	Remote Similarity	NPD8377	Phase 4
0.6	Remote Similarity	NPD8335	Phase 4
0.5758	Remote Similarity	NPD8296	Phase 4
0.567	Remote Similarity	NPD7507	Pre-clinical
0.5625	Remote Similarity	NPD7319	Approved
0.5612	Remote Similarity	NPD8380	Approved
0.5577	Remote Similarity	NPD8378	Pre-clinical
0.5577	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