NPASS Compound

Natural Product: NPC486137

Natural Product ID	NPC486137
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	XTMNBZGYPGOXQO-UKKXKDGESA-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 106112 0 0 0 0 0 0 0 0999 V2000 -4.9671 -2.6198 0.8664 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2396 -1.3671 0.3999 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.1815 -0.5936 -0.4899 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4476 0.0040 -1.6787 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1437 0.5548 -1.0842 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3371 -0.6767 -0.7141 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0858 -1.7275 -0.2590 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3020 -0.3671 0.1562 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0566 -0.5671 -0.4342 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7165 -1.6354 0.2512 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7926 -1.2522 1.1699 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5538 0.0166 0.8329 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1176 1.0113 1.9218 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4501 0.5430 3.1918 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1303 0.6172 -0.4670 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5064 -0.1908 -1.6840 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7528 -1.0290 -1.4639 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6188 -0.2305 -0.5360 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0413 -0.2024 0.8753 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8450 0.7630 1.6514 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8954 1.5032 0.8259 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8119 0.6013 0.0650 C 0 0 1 0 0 0 0 0 0 0 0 0 7.4050 1.3777 -1.0881 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9079 0.0103 0.8911 C 0 0 1 0 0 0 0 0 0 0 0 0 8.0143 -1.4217 0.3454 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5139 -1.7352 0.2108 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0582 -0.5623 -0.5652 C 0 0 1 0 0 0 0 0 0 0 0 0 6.4298 -0.7574 -1.9028 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1994 0.7172 0.7038 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3173 0.2311 0.1434 C 0 0 0 0 0 0 0 0 0 0 0 0 11.3602 1.2469 0.1533 C 0 0 0 0 0 0 0 0 0 0 0 0 12.5497 1.1384 -0.2946 O 0 0 0 0 0 0 0 0 0 0 0 0 10.8179 2.3581 0.7424 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4736 2.1069 1.1239 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6173 0.7597 -0.5394 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4596 1.2184 -2.0938 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0745 -0.9807 -2.5894 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5428 -0.7021 -3.8724 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9094 0.3670 0.1938 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2642 0.2238 0.1746 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.7866 0.1090 1.5847 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.2227 -0.3588 1.4760 C 0 0 2 0 0 0 0 0 0 0 0 0 -10.0017 0.3998 0.4457 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.2058 0.8851 -0.7109 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.9229 2.1006 -1.3109 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2161 1.7913 -1.6874 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9292 1.3260 -0.3761 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.9910 -0.4800 -0.0437 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.8399 -0.1307 2.7186 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0695 -0.7219 2.4020 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8182 -2.7485 1.9555 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0345 -2.5421 0.6216 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5546 -3.4897 0.3118 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9368 -0.7863 1.2963 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9023 -1.3145 -0.9211 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0225 0.7570 -2.2065 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3351 1.1995 -0.2110 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8916 -1.0209 -1.6979 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2499 -0.9372 -1.4860 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0423 -2.2412 0.8392 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1082 -2.4070 -0.4801 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4174 -1.2545 2.2358 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5640 -2.0803 1.1941 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9883 0.9517 1.9130 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3786 2.0380 1.7095 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0314 -0.2530 3.1510 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5433 1.6488 -0.5102 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6799 -0.7563 -2.1217 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8034 0.5661 -2.4700 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3072 -1.1453 -2.4207 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5142 -2.0406 -1.0859 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5356 0.8456 -0.8835 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1933 -1.2275 1.3276 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4497 0.2526 2.4600 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2918 1.5526 2.1830 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5323 2.0392 1.5891 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4491 2.3012 0.2125 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5111 1.3209 -1.1250 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1548 2.4489 -0.9665 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9816 1.0768 -2.0750 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6337 -0.0202 1.9486 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5036 -1.4375 -0.6272 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4821 -2.0485 1.1195 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1447 -1.8055 1.2448 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4173 -2.7098 -0.3009 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4537 -1.7228 -2.1205 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4486 -0.7577 -0.2599 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4693 2.1277 2.2363 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8418 2.8688 0.6721 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2174 1.5337 0.1430 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4324 1.1987 -1.5672 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3952 2.2000 -1.9417 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2032 -1.5294 -4.5246 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0417 0.2154 -4.2924 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6319 -0.6353 -3.9169 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5202 -0.6887 -0.3873 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8228 1.1696 1.9764 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2249 -1.4287 1.2666 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5755 1.2549 0.9016 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1286 0.1451 -1.5491 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9411 2.8881 -0.5138 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3570 2.5063 -2.1823 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.4244 2.3539 -2.4888 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.8151 0.0269 -0.2636 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6464 -0.6961 2.7450 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6642 -1.4345 2.7492 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 13 14 1 0 12 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 0 22 23 1 6 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 6 24 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 1 0 15 35 1 0 5 36 1 0 4 37 1 0 37 38 1 0 3 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 45 46 1 0 44 47 1 0 43 48 1 0 42 49 1 0 41 50 1 0 7 2 1 0 35 9 1 0 47 40 1 0 19 12 1 0 27 22 1 0 34 29 1 0 27 18 1 0 1 51 1 0 1 52 1 0 1 53 1 0 2 54 1 1 3 55 1 6 4 56 1 6 5 57 1 1 6 58 1 6 9 59 1 6 10 60 1 0 10 61 1 0 11 62 1 0 11 63 1 0 13 64 1 0 13 65 1 0 14 66 1 0 15 67 1 6 16 68 1 0 16 69 1 0 17 70 1 0 17 71 1 0 18 72 1 6 19 73 1 1 20 74 1 0 20 75 1 0 21 76 1 0 21 77 1 0 23 78 1 0 23 79 1 0 23 80 1 0 24 81 1 1 25 82 1 0 25 83 1 0 26 84 1 0 26 85 1 0 28 86 1 0 30 87 1 0 34 88 1 0 34 89 1 0 35 90 1 0 35 91 1 0 36 92 1 0 38 93 1 0 38 94 1 0 38 95 1 0 40 96 1 6 41 97 1 1 42 98 1 6 43 99 1 1 44100 1 6 45101 1 0 45102 1 0 46103 1 0 48104 1 0 49105 1 0 50106 1 0 M END

Standard InCHIKey	XTMNBZGYPGOXQO-UKKXKDGESA-N
Standard InCHI	InChI=1S/C36H56O14/c1-17-30(50-32-28(42)27(41)26(40)24(14-37)49-32)31(45-3)29(43)33(47-17)48-20-6-10-35(16-38)19(13-20)4-5-23-22(35)7-9-34(2)21(8-11-36(23,34)44)18-12-25(39)46-15-18/h12,17,19-24,26-33,37-38,40-44H,4-11,13-16H2,1-3H3/t17-,19+,20-,21+,22-,23+,24-,26-,27+,28-,29+,30-,31-,32+,33-,34+,35+,36-/m1/s1
SMILES	C[C@@H]1[C@H]([C@@H]([C@@H]([C@H](O1)O[C@@H]1CC[C@]2(CO)[C@@H](CC[C@H]3[C@H]2CC[C@@]2(C)[C@@H](CC[C@@]32O)C2=CC(=O)OC2)C1)O)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:	712.37	Volume:	689.107 ? Van der Waals volume.
Dense:	1.034	LogP:	0.304 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.088 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.656 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	38.0
TPSA:	214.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	7.0	Rings:	7.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.129	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.729	Fsp³:	0.917
MCE-18:	132.145 ? 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:	0.726	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.013 ? 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:	0.16	Promiscuous compounds:	0.261

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.426	MDCK Permeability:	-5.219
Pgp-inhibitor:	0.0	Pgp-substrate:	0.931
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):	0.872
20% Bioavailability (F20%):	0.562	30% Bioavailability (F30%):	0.983
50% Bioavailability (F50%):	0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.013	MRP1:	0.306
Plasma Protein Binding (PPB):	50.007%	Volume Distribution (VD):	-0.496
Fu:	47.354% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.004
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.867	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.131	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.758	CYP3A4-substrate:	0.064
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.003
HLM stability:	0.004 ? 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):

1.156

Half-life (T1/2):

3.505

ADMET: Toxicity

hERG Blockers:	0.031	hERG Blockers (10um):	0.098
Human Hepatotoxicity (H-HT):	0.911	Drug-induced Liver Injury (DILI):	0.889
AMES Toxicity:	0.96	Rat Oral Acute Toxicity:	0.121
Maximum Recommended Daily Dose:	0.856	Skin Sensitization:	1.0
Carcinogencity:	0.915	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.244
Drug-induced Neurotoxicity:	0.009	Ototoxicity:	0.985
Hematotoxicity:	0.663	Drug-induced Nephrotoxicity:	0.995
Genotoxicity:	0.843	RPMI-8226 Immunitoxicity:	0.431
A549 Cytotoxicity:	0.907	Hek293 Cytotoxicity:	0.843
BCF:	0.582 ? 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:	3.252 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.653 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.786 ? 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
NPO8402	Thevetia peruviana	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26714048]
NPO8402	Thevetia peruviana	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39027575]
NPO8402	Thevetia peruviana	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8402	Thevetia peruviana	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

Activity Type	# Activity
IC50	4

Activity Type	# Activity
Cell line	1
Non-molecular	2
Others	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
NPT1312	Cell line	SW1990	Homo sapiens	IC50	=	2140.0	nM	PMID[26714048]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	4910.0	nM	PMID[26714048]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	5750.0	nM	PMID[26714048]
NPT27	Others	Unspecified	n.a.	IC50	>	10000.0	nM	PMID[26714048]

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 NPC486137 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	14110
0.1-0.2	30140
0.2-0.3	4533
0.3-0.4	858
0.4-0.5	69
0.5-0.6	56
0.6-0.7	42
0.7-0.8	1
0.8-0.85	9
0.85-0.9	7
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC486135
0.9302	High Similarity	NPC486136
0.8824	High Similarity	NPC486143
0.8824	High Similarity	NPC486142
0.8824	High Similarity	NPC486149
0.8721	High Similarity	NPC232785
0.8721	High Similarity	NPC486139
0.8625	High Similarity	NPC77299
0.8625	High Similarity	NPC480906
0.8471	Intermediate Similarity	NPC32177
0.8471	Intermediate Similarity	NPC469756
0.8471	Intermediate Similarity	NPC275901
0.8242	Intermediate Similarity	NPC486144
0.8242	Intermediate Similarity	NPC486145
0.8242	Intermediate Similarity	NPC486147
0.8242	Intermediate Similarity	NPC486148
0.8161	Intermediate Similarity	NPC480910
0.8161	Intermediate Similarity	NPC480909
0.7872	Intermediate Similarity	NPC120390
0.7865	Intermediate Similarity	NPC475629
0.7857	Intermediate Similarity	NPC76572
0.7857	Intermediate Similarity	NPC193382
0.7753	Intermediate Similarity	NPC486130
0.7667	Intermediate Similarity	NPC486127
0.7551	Intermediate Similarity	NPC474423
0.7529	Intermediate Similarity	NPC5311
0.7473	Intermediate Similarity	NPC231518
0.7473	Intermediate Similarity	NPC488944
0.7444	Intermediate Similarity	NPC236973
0.7442	Intermediate Similarity	NPC480914
0.7419	Intermediate Similarity	NPC329986
0.7419	Intermediate Similarity	NPC140092
0.7363	Intermediate Similarity	NPC188234
0.7273	Intermediate Similarity	NPC305574
0.7263	Intermediate Similarity	NPC486132
0.7263	Intermediate Similarity	NPC486131
0.7234	Intermediate Similarity	NPC486146
0.7188	Intermediate Similarity	NPC486128
0.7158	Intermediate Similarity	NPC486138
0.7158	Intermediate Similarity	NPC276838
0.7143	Intermediate Similarity	NPC475419
0.7143	Intermediate Similarity	NPC30483
0.7143	Intermediate Similarity	NPC470897
0.7111	Intermediate Similarity	NPC480907
0.701	Intermediate Similarity	NPC479360
0.701	Intermediate Similarity	NPC479359
0.701	Intermediate Similarity	NPC488943
0.701	Intermediate Similarity	NPC488942
0.6989	Remote Similarity	NPC240070
0.69	Remote Similarity	NPC486140
0.69	Remote Similarity	NPC486134
0.69	Remote Similarity	NPC486141
0.6889	Remote Similarity	NPC483822
0.6882	Remote Similarity	NPC292467
0.6842	Remote Similarity	NPC125077
0.6832	Remote Similarity	NPC486133
0.6832	Remote Similarity	NPC486150
0.6809	Remote Similarity	NPC479353
0.6809	Remote Similarity	NPC479354
0.68	Remote Similarity	NPC74259
0.6737	Remote Similarity	NPC488941
0.6737	Remote Similarity	NPC488940
0.6733	Remote Similarity	NPC474908
0.6705	Remote Similarity	NPC99620
0.6629	Remote Similarity	NPC84987
0.6602	Remote Similarity	NPC488945
0.6602	Remote Similarity	NPC488946
0.66	Remote Similarity	NPC475590
0.6556	Remote Similarity	NPC469750
0.6531	Remote Similarity	NPC146857
0.6522	Remote Similarity	NPC471353
0.6509	Remote Similarity	NPC486152
0.6458	Remote Similarity	NPC32793
0.6458	Remote Similarity	NPC116075
0.64	Remote Similarity	NPC479357
0.625	Remote Similarity	NPC329675
0.625	Remote Similarity	NPC194716
0.6129	Remote Similarity	NPC199428
0.6129	Remote Similarity	NPC109448
0.6129	Remote Similarity	NPC310341
0.6122	Remote Similarity	NPC475556
0.6122	Remote Similarity	NPC311706
0.61	Remote Similarity	NPC469749
0.6087	Remote Similarity	NPC196429
0.6064	Remote Similarity	NPC250556
0.6061	Remote Similarity	NPC264336
0.6022	Remote Similarity	NPC157376
0.6022	Remote Similarity	NPC142066
0.6022	Remote Similarity	NPC603972
0.6	Remote Similarity	NPC208193
0.5943	Remote Similarity	NPC117445
0.5943	Remote Similarity	NPC308262
0.5888	Remote Similarity	NPC329784
0.5882	Remote Similarity	NPC247190
0.5876	Remote Similarity	NPC72260
0.5865	Remote Similarity	NPC488938
0.5865	Remote Similarity	NPC488937
0.5806	Remote Similarity	NPC99728
0.5806	Remote Similarity	NPC87250
0.5806	Remote Similarity	NPC244402
0.5806	Remote Similarity	NPC50305
0.5806	Remote Similarity	NPC471633
0.5789	Remote Similarity	NPC84949
0.5789	Remote Similarity	NPC480562
0.5789	Remote Similarity	NPC74945
0.5789	Remote Similarity	NPC31354
0.5789	Remote Similarity	NPC69576
0.57	Remote Similarity	NPC40749
0.5686	Remote Similarity	NPC59288
0.5686	Remote Similarity	NPC55532
0.5684	Remote Similarity	NPC17896
0.5684	Remote Similarity	NPC469755
0.5684	Remote Similarity	NPC284406
0.5684	Remote Similarity	NPC197707
0.5684	Remote Similarity	NPC251866
0.5684	Remote Similarity	NPC480915
0.5636	Remote Similarity	NPC488947
0.5588	Remote Similarity	NPC610296
0.5577	Remote Similarity	NPC488939
0.5517	Remote Similarity	NPC222875
0.5517	Remote Similarity	NPC25177
0.551	Remote Similarity	NPC179412
0.551	Remote Similarity	NPC484202
0.551	Remote Similarity	NPC93883
0.551	Remote Similarity	NPC471356
0.5472	Remote Similarity	NPC476221
0.5472	Remote Similarity	NPC477709
0.5472	Remote Similarity	NPC475219
0.5464	Remote Similarity	NPC243196
0.5408	Remote Similarity	NPC146456
0.5368	Remote Similarity	NPC158344
0.5312	Remote Similarity	NPC473852
0.5263	Remote Similarity	NPC286809
0.5258	Remote Similarity	NPC219085
0.5258	Remote Similarity	NPC486129
0.5229	Remote Similarity	NPC479358
0.5227	Remote Similarity	NPC480913
0.5204	Remote Similarity	NPC486126
0.5102	Remote Similarity	NPC309034
0.5098	Remote Similarity	NPC329905
0.5096	Remote Similarity	NPC27363
0.5052	Remote Similarity	NPC474418
0.5051	Remote Similarity	NPC479356
0.5051	Remote Similarity	NPC34390
0.5051	Remote Similarity	NPC479355
0.5049	Remote Similarity	NPC173555

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC486137 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5945
0.1-0.2	3095
0.2-0.3	90
0.3-0.4	6
0.4-0.5	7
0.5-0.6	5
0.6-0.7	1
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
0.7473	Intermediate Similarity	NPD8033	Approved
0.6064	Remote Similarity	NPD7507	Pre-clinical
0.5876	Remote Similarity	NPD8294	Phase 4
0.5684	Remote Similarity	NPD7319	Approved
0.5385	Remote Similarity	NPD8377	Phase 4
0.51	Remote Similarity	NPD8335	Phase 4
0.5049	Remote Similarity	NPD8296	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