NPASS Compound

Natural Product: NPC266728

Natural Product ID	NPC266728
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3S,4S,5R)-4-[(2R,3R)-2,3-Dihydroxy-3-[(2S,3R,5R,10R,13R,14S)-2,3,14-Trihydroxy-10,13-Dimethyl-6-Oxo-2,3,4,5,9,11,12,15,16,17-Decahydro-1H-Cyclopenta[A]Phenanthren-17-Yl]Butyl]-3,5-Dimethyloxolan-2-One
IUPAC Name	(3S,4S,5R)-4-[(2R,3R)-2,3-dihydroxy-3-[(2S,3R,5R,10R,13R,14S)-2,3,14-trihydroxy-10,13-dimethyl-6-oxo-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]butyl]-3,5-dimethyloxolan-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1736717
PubChem CID	44201988
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 81 85 0 0 0 0 0 0 0 0999 V2000 7.7779 0.9613 -1.3442 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5176 1.0610 -0.4569 C 0 0 1 0 0 0 0 0 0 0 0 0 5.5971 -0.0609 -0.6813 C 0 0 2 0 0 0 0 0 0 0 0 0 4.1231 0.2431 -0.7893 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4993 0.8545 0.3953 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9981 1.1396 0.2997 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7191 2.0803 -0.7842 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1571 -0.0668 0.4849 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3305 -1.2117 -0.4747 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0190 -1.9946 -0.2036 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9141 -0.8463 -0.2404 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3133 -1.1481 0.0301 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8249 -2.3082 -0.2995 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2503 -2.5650 -0.0048 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6554 -3.6906 0.2953 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1448 -1.3800 -0.0969 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7325 -1.2822 -1.5176 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8536 -0.2686 -1.4452 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.4080 1.0464 -0.8931 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8972 0.9611 -0.6714 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5558 -0.1017 0.3707 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.3479 0.3444 1.6171 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1040 -0.0798 0.6949 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4707 1.2174 0.3537 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9999 1.3170 0.7390 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2672 0.0606 0.8133 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5471 -0.5657 2.1951 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0953 1.4833 0.2134 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8932 -0.7553 -0.6494 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7382 -0.2456 -1.5087 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7928 1.8691 1.5383 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1720 2.1050 0.5645 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8497 -1.0184 0.4939 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9966 -1.9569 0.2116 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2449 -0.1182 1.5043 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0035 0.8646 0.9223 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9470 1.5017 1.4394 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4578 0.9143 -2.3924 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3280 0.0735 -0.9854 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3337 1.9101 -1.1217 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1183 2.0849 -0.5310 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8986 -0.6208 -1.5895 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0904 1.0370 -1.6163 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6710 -0.6251 -1.2519 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6580 0.2267 1.2883 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3838 3.0995 -0.4516 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6970 2.3484 -1.3054 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0602 1.7826 -1.5968 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6418 -0.5324 1.4305 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2872 -0.9478 -1.5273 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1782 -1.8984 -0.2034 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0798 -2.5105 0.7771 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1465 -2.7089 -1.0391 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2310 -3.0656 -0.7717 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0343 -1.6413 0.5214 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2102 -2.2687 -1.6938 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9897 -1.0901 -2.2807 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2225 -0.1148 -2.5035 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5093 1.8528 -1.6820 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5390 1.9734 -0.3673 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4664 0.7671 -1.6499 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3350 1.4339 1.7408 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3172 -0.1456 1.6863 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7485 -0.0550 2.4885 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0347 -0.1803 1.8208 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0062 2.0204 0.9415 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6217 1.4113 -0.7280 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9458 1.8139 1.7600 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6370 2.0927 0.0330 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4551 -0.8499 2.6459 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0827 -1.5122 2.1226 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9428 0.1772 2.9036 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9793 2.4642 0.2881 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0984 -0.1451 0.0756 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9526 -0.9186 -2.2062 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2658 2.6709 1.3643 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9405 2.4399 1.4702 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9115 -1.5588 0.7380 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9562 -1.6194 0.6564 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7572 -3.0057 0.5115 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1485 -2.0054 -0.8853 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 2 0 13 14 1 0 14 15 2 0 14 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 1 19 28 1 0 18 29 1 0 11 30 1 6 6 31 1 1 5 32 1 0 3 33 1 0 33 34 1 0 33 35 1 0 35 36 1 0 36 37 2 0 36 2 1 0 26 8 1 0 26 11 1 0 23 12 1 0 21 16 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 1 3 42 1 6 4 43 1 0 4 44 1 0 5 45 1 1 7 46 1 0 7 47 1 0 7 48 1 0 8 49 1 0 9 50 1 0 9 51 1 0 10 52 1 0 10 53 1 0 13 54 1 0 16 55 1 1 17 56 1 0 17 57 1 0 18 58 1 6 19 59 1 6 20 60 1 0 20 61 1 0 22 62 1 0 22 63 1 0 22 64 1 0 23 65 1 0 24 66 1 0 24 67 1 0 25 68 1 0 25 69 1 0 27 70 1 0 27 71 1 0 27 72 1 0 28 73 1 0 29 74 1 0 30 75 1 0 31 76 1 0 32 77 1 0 33 78 1 1 34 79 1 0 34 80 1 0 34 81 1 0 M END

Standard InCHIKey	NEFYSBQJYCICOG-VHVOLZJXSA-N
Standard InCHI	InChI=1S/C29H44O8/c1-14-16(15(2)37-25(14)34)10-24(33)28(5,35)23-7-9-29(36)18-11-20(30)19-12-21(31)22(32)13-26(19,3)17(18)6-8-27(23,29)4/h11,14-17,19,21-24,31-33,35-36H,6-10,12-13H2,1-5H3/t14-,15+,16-,17?,19-,21+,22-,23?,24+,26+,27+,28+,29+/m0/s1
SMILES	C[C@H]1[C@H](C[C@H]([C@@](C)(C2CC[C@]3(C4=CC(=O)[C@@H]5C[C@H]([C@H](C[C@]5(C)C4CC[C@]23C)O)O)O)O)O)[C@@H](C)OC1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	520.3	Volume:	529.77 ? Van der Waals volume.
Dense:	0.982	LogP:	1.557 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.144 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.469 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	27.0
TPSA:	144.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	5.0	Rings:	5.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.354	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.522	Fsp³:	0.862
MCE-18:	102.556 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.203	Fluc inhibitor:	0.008 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.016 ? 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:	0.224	Promiscuous compounds:	0.365

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.884	MDCK Permeability:	-4.524
Pgp-inhibitor:	0.0	Pgp-substrate:	0.683
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):	0.029
20% Bioavailability (F20%):	0.907	30% Bioavailability (F30%):	0.838
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.824
Plasma Protein Binding (PPB):	88.258%	Volume Distribution (VD):	0.109
Fu:	11.462% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.036
BSEP inhibitor:	0.898

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.098	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.388
HLM stability:	0.498 ? 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):

5.017

Half-life (T1/2):

2.745

ADMET: Toxicity

hERG Blockers:	0.031	hERG Blockers (10um):	0.304
Human Hepatotoxicity (H-HT):	0.739	Drug-induced Liver Injury (DILI):	0.045
AMES Toxicity:	0.104	Rat Oral Acute Toxicity:	0.278
Maximum Recommended Daily Dose:	0.931	Skin Sensitization:	0.9
Carcinogencity:	0.943	Eye Corrosion:	0.0
Eye Irritation:	0.045	Respiratory Toxicity:	0.297
Drug-induced Neurotoxicity:	0.108	Ototoxicity:	0.917
Hematotoxicity:	0.053	Drug-induced Nephrotoxicity:	0.841
Genotoxicity:	0.956	RPMI-8226 Immunitoxicity:	0.099
A549 Cytotoxicity:	0.233	Hek293 Cytotoxicity:	0.585
BCF:	0.495 ? 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:	3.188 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.792 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.867 ? 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
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	flowering whole plant	n.a.	n.a.	PMID[10425119]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15043410]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	whole plants	Zhejiang Province, China	2008-AUG	PMID[21682262]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[21682262]
NPO16818	Trillium tschonoskii	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32870000]
NPO11283	Ajuga chamaepitys	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38732407]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9748375]
NPO11283	Ajuga chamaepitys	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7849	Ajuga taiwanensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3975	Cyathula capitata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16818	Trillium tschonoskii	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16818	Trillium tschonoskii	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2775	Cyathula officinalis	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7849	Ajuga taiwanensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11283	Ajuga chamaepitys	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3975	Cyathula capitata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6471	Trillium camtschaticum	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11283	Ajuga chamaepitys	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3975	Cyathula capitata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16818	Trillium tschonoskii	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7849	Ajuga taiwanensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6471	Trillium camtschaticum	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2775	Cyathula officinalis	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3975	Cyathula capitata	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16818	Trillium tschonoskii	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO6471	Trillium camtschaticum	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2775	Cyathula officinalis	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11283	Ajuga chamaepitys	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2775	Cyathula officinalis	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1048	Ajuga reptans	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6471	Trillium camtschaticum	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16818	Trillium tschonoskii	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2775	Cyathula officinalis	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17539	Ajuga decumbens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11283	Ajuga chamaepitys	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7849	Ajuga taiwanensis	Species	Lamiaceae	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
Potency	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	16353.5	nM	PubChem BioAssay data set

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 NPC266728 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	17857
0.1-0.2	27298
0.2-0.3	4634
0.3-0.4	16
0.4-0.5	8
0.5-0.6	14
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
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	NPC49492
0.8358	Intermediate Similarity	NPC109973
0.7812	Intermediate Similarity	NPC214264
0.7812	Intermediate Similarity	NPC475060
0.7812	Intermediate Similarity	NPC85829
0.7692	Intermediate Similarity	NPC296945
0.7538	Intermediate Similarity	NPC50692
0.7538	Intermediate Similarity	NPC260268
0.7538	Intermediate Similarity	NPC48733
0.7538	Intermediate Similarity	NPC171137
0.7538	Intermediate Similarity	NPC152695
0.7538	Intermediate Similarity	NPC319077
0.7538	Intermediate Similarity	NPC83744
0.7538	Intermediate Similarity	NPC97202
0.7538	Intermediate Similarity	NPC601752
0.7424	Intermediate Similarity	NPC220229
0.7424	Intermediate Similarity	NPC601682
0.7353	Intermediate Similarity	NPC476027
0.7286	Intermediate Similarity	NPC600136
0.7206	Intermediate Similarity	NPC202167
0.7206	Intermediate Similarity	NPC49958
0.7	Intermediate Similarity	NPC222688
0.6761	Remote Similarity	NPC207251
0.662	Remote Similarity	NPC317210
0.6618	Remote Similarity	NPC302607
0.6533	Remote Similarity	NPC475041
0.6286	Remote Similarity	NPC76084
0.6143	Remote Similarity	NPC600374
0.6056	Remote Similarity	NPC149047
0.6	Remote Similarity	NPC150531
0.6	Remote Similarity	NPC250109
0.5915	Remote Similarity	NPC204833
0.5915	Remote Similarity	NPC209502
0.5915	Remote Similarity	NPC477915
0.5833	Remote Similarity	NPC329417
0.5696	Remote Similarity	NPC600372
0.5694	Remote Similarity	NPC11710
0.5694	Remote Similarity	NPC217201
0.5694	Remote Similarity	NPC451956
0.5694	Remote Similarity	NPC610677
0.5584	Remote Similarity	NPC606024
0.5507	Remote Similarity	NPC603391
0.5244	Remote Similarity	NPC606413
0.5233	Remote Similarity	NPC28532
0.519	Remote Similarity	NPC326542

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC266728 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6407
0.1-0.2	2575
0.2-0.3	168
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
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
		NPD

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