NPASS Compound

Natural Product: NPC541670

Natural Product ID	NPC541670
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(3,7,12,16,20,24-hexamethylpentacosa-1,3,5,7,9,11,15,19,23-nonaenyl)-1,3,3-trimethyl-cyclohexene
IUPAC Name	2-(3,7,12,16,20,24-hexamethylpentacosa-1,3,5,7,9,11,15,19,23-nonaenyl)-1,3,3-trimethyl-cyclohexene
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:0000259] Prenol lipids [CHEMONTID:0001554] Tetraterpenoids [CHEMONTID:0001277] Carotenoids [CHEMONTID:0001411] Carotenes

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 100100 0 0 0 0 0 0 0 0999 V2000 12.0598 0.2688 -1.0961 C 0 0 0 0 0 0 0 0 0 0 0 0 11.5922 -1.1246 -1.0024 C 0 0 0 0 0 0 0 0 0 0 0 0 12.5761 -2.1098 -0.4197 C 0 0 0 0 0 0 0 0 0 0 0 0 10.4175 -1.5558 -1.3660 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3289 -0.7256 -1.9413 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0870 -0.7924 -1.0666 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3769 -0.2992 0.3227 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8395 1.1071 0.4633 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2197 -1.1060 1.3413 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4376 -0.8391 2.7681 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1197 -1.1607 3.4779 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0490 -0.2468 3.0214 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2306 1.2212 3.3465 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9601 -0.5815 2.3751 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5132 -1.8955 1.9390 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2410 -2.4212 2.4981 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0608 -1.5699 2.3526 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9486 -0.2709 3.1115 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0007 -1.9026 1.6055 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1170 -0.9782 1.5340 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1890 -1.1846 0.8226 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4490 -2.3260 0.0058 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5631 -2.4965 -0.7258 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6977 -3.7335 -1.5317 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6003 -1.5225 -0.6969 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7199 -1.5819 -1.4115 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6453 -0.4872 -1.2310 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7787 -0.3659 -1.8867 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2462 -1.3152 -2.8804 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6071 0.8224 -1.5222 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7230 1.0827 -2.1188 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6873 2.1518 -1.9361 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7646 2.1632 -2.7672 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.8913 1.0993 -3.7848 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.7224 3.2771 -2.6616 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.1985 3.4042 -1.2438 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.0938 3.2919 -0.2667 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7017 3.2171 -0.9226 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2621 4.5520 -1.4530 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7813 2.8928 0.2382 C 0 0 0 0 0 0 0 0 0 0 0 0 12.3379 0.6475 -0.0643 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3598 0.9903 -1.5357 H 0 0 0 0 0 0 0 0 0 0 0 0 12.9836 0.3370 -1.7539 H 0 0 0 0 0 0 0 0 0 0 0 0 13.2705 -2.4063 -1.2150 H 0 0 0 0 0 0 0 0 0 0 0 0 13.1632 -1.5901 0.3576 H 0 0 0 0 0 0 0 0 0 0 0 0 12.0419 -2.9895 0.0129 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2381 -2.6527 -1.2159 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0549 -1.2265 -2.9188 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6769 0.2597 -2.1763 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2114 -0.3109 -1.4982 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8720 -1.8869 -0.9694 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0890 1.8065 0.8230 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6921 1.1466 1.2082 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2671 1.4421 -0.5162 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8706 -2.1356 1.0725 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2970 -1.3557 3.1907 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5922 0.2540 2.9062 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3057 -0.9354 4.5622 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8629 -2.1847 3.2529 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0925 1.3168 4.0104 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3175 1.7661 2.3867 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2817 1.6135 3.8003 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2740 0.2578 2.0938 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3143 -2.6806 2.0533 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3779 -1.8411 0.8179 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4251 -2.6145 3.5936 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0108 -3.4443 2.0940 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9090 0.5346 2.3735 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0111 -0.2518 3.7245 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7998 -0.1271 3.8083 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9483 -2.8188 1.0607 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0531 -0.0396 2.1210 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9623 -0.3878 0.8698 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7026 -3.1276 -0.0497 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6156 -4.5877 -0.8205 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6854 -3.7986 -1.9927 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9229 -3.8260 -2.3240 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5055 -0.6360 -0.0357 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9753 -2.3591 -2.0977 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3916 0.2891 -0.5095 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7077 -1.1632 -3.8615 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3250 -1.3985 -2.9988 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9172 -2.3587 -2.5537 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1224 1.4044 -0.7369 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9913 0.3647 -2.9241 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9345 0.0936 -3.3439 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.8303 1.3149 -4.3626 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0007 1.1952 -4.4693 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.5720 3.0735 -3.3634 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.2503 4.2066 -3.0449 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.9647 2.5906 -1.1016 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.7360 4.3650 -1.1334 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0999 4.1738 0.3997 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.2032 2.3343 0.3020 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3703 4.9612 -0.8837 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0603 5.2792 -1.2870 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9254 4.4332 -2.4995 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7875 3.2913 0.0236 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7994 1.8634 0.5666 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1559 3.5701 1.0956 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 2 3 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 7 9 2 3 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 12 14 2 3 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 2 3 19 20 1 0 20 21 2 3 21 22 1 0 22 23 2 3 23 24 1 0 23 25 1 0 25 26 2 3 26 27 1 0 27 28 2 3 28 29 1 0 28 30 1 0 30 31 2 3 31 32 1 0 32 33 2 0 33 34 1 0 33 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 38 40 1 0 38 32 1 0 1 41 1 0 1 42 1 0 1 43 1 0 3 44 1 0 3 45 1 0 3 46 1 0 4 47 1 0 5 48 1 0 5 49 1 0 6 50 1 0 6 51 1 0 8 52 1 0 8 53 1 0 8 54 1 0 9 55 1 0 10 56 1 0 10 57 1 0 11 58 1 0 11 59 1 0 13 60 1 0 13 61 1 0 13 62 1 0 14 63 1 0 15 64 1 0 15 65 1 0 16 66 1 0 16 67 1 0 18 68 1 0 18 69 1 0 18 70 1 0 19 71 1 0 20 72 1 0 21 73 1 0 22 74 1 0 24 75 1 0 24 76 1 0 24 77 1 0 25 78 1 0 26 79 1 0 27 80 1 0 29 81 1 0 29 82 1 0 29 83 1 0 30 84 1 0 31 85 1 0 34 86 1 0 34 87 1 0 34 88 1 0 35 89 1 0 35 90 1 0 36 91 1 0 36 92 1 0 37 93 1 0 37 94 1 0 39 95 1 0 39 96 1 0 39 97 1 0 40 98 1 0 40 99 1 0 40100 1 0 M END

Standard InCHIKey	CJPVGWWWFOEZJV-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C40H60/c1-32(2)18-13-21-35(5)24-15-26-36(6)25-14-22-33(3)19-11-12-20-34(4)23-16-27-37(7)29-30-39-38(8)28-17-31-40(39,9)10/h11-12,16,18-20,23-25,27,29-30H,13-15,17,21-22,26,28,31H2,1-10H3
SMILES	CC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CC=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	540.47	Volume:	665.475 ? Van der Waals volume.
Dense:	0.812	LogP:	15.065 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	8.003 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-10.992 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	15.0
TPSA:	0.0 ? Topological Polar Surface Area.	H-Bond Acceptor:	0.0
H-Bond Donor:	0.0	Rings:	1.0
Heavy Atoms:	0.0

MedChem Properties

QED Drug-Likeness Score:	0.143	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.72	Fsp³:	0.5
MCE-18:	15.867 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.666 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.001 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.007 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.674	Promiscuous compounds:	0.152

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.732	MDCK Permeability:	-4.748
Pgp-inhibitor:	0.991	Pgp-substrate:	0.055
PAMPA:	0.009 ? 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%):	0.001	30% Bioavailability (F30%):	0.002
50% Bioavailability (F50%):	0.724

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.998	MRP1:	0.999
Plasma Protein Binding (PPB):	96.955%	Volume Distribution (VD):	0.407
Fu:	2.791% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.984
OATP1B3 inhibitor:	0.155	BCRP inhibitor:	0.013
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.099
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.973	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.995	CYP3A4-substrate:	1.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

8.613

Half-life (T1/2):

0.226

ADMET: Toxicity

hERG Blockers:	0.238	hERG Blockers (10um):	0.675
Human Hepatotoxicity (H-HT):	0.345	Drug-induced Liver Injury (DILI):	0.028
AMES Toxicity:	0.273	Rat Oral Acute Toxicity:	0.307
Maximum Recommended Daily Dose:	0.784	Skin Sensitization:	1.0
Carcinogencity:	0.563	Eye Corrosion:	0.094
Eye Irritation:	0.788	Respiratory Toxicity:	0.91
Drug-induced Neurotoxicity:	0.686	Ototoxicity:	0.399
Hematotoxicity:	0.216	Drug-induced Nephrotoxicity:	0.685
Genotoxicity:	0.006	RPMI-8226 Immunitoxicity:	0.121
A549 Cytotoxicity:	0.228	Hek293 Cytotoxicity:	0.289
BCF:	3.242 ? 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:	6.101 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.313 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	8.715 ? 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
NPO11114	Phycomyces blakesleeanus	Species	Phycomycetaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9868149]
NPO13966	Coccinella septempunctata	Species	Coccinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13763	Dioscorea prazeri	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13662	Elysia timida	Species	Placobranchidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5117	Gyalolechia fulgens	Species	Teloschistaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13573	Medicago scutellata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11114	Phycomyces blakesleeanus	Species	Phycomycetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13866	Sterculia setigera	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13866	Sterculia setigera	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13573	Medicago scutellata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5117	Gyalolechia fulgens	Species	Teloschistaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13966	Coccinella septempunctata	Species	Coccinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11114	Phycomyces blakesleeanus	Species	Phycomycetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13662	Elysia timida	Species	Placobranchidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13763	Dioscorea prazeri	Species	Dioscoreaceae	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 NPC541670 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	39694
0.1-0.2	9603
0.2-0.3	490
0.3-0.4	50
0.4-0.5	6
0.5-0.6	8
0.6-0.7	2
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	Natural Product ID
0.7105	Intermediate Similarity	NPC17810
0.7105	Intermediate Similarity	NPC606095
0.6316	Remote Similarity	NPC99088
0.6316	Remote Similarity	NPC173592
0.5909	Remote Similarity	NPC22019
0.5909	Remote Similarity	NPC281986
0.5909	Remote Similarity	NPC321568
0.5778	Remote Similarity	NPC55412
0.5778	Remote Similarity	NPC249645
0.5294	Remote Similarity	NPC254886
0.5263	Remote Similarity	NPC305759
0.5098	Remote Similarity	NPC226066

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC541670 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8770
0.1-0.2	351
0.2-0.3	13
0.3-0.4	5
0.4-0.5	4
0.5-0.6	2
0.6-0.7	0
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
0.7105	Intermediate Similarity	NPD8262	Phase 4
0.5778	Remote Similarity	NPD4219	Phase 4
0.5098	Remote Similarity	NPD5325	Clinical (unspecified phase)

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