NPASS Compound

Natural Product: NPC257390

Natural Product ID	NPC257390
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3S,6S)-3,6-Bis-(4-Hydroxy-Benzyl)-1,4-Dimethyl-Piperazine-2,5-Dione
IUPAC Name	(3S,6S)-3,6-bis[(4-hydroxyphenyl)methyl]-1,4-dimethylpiperazine-2,5-dione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL89560
PubChem CID	10473315
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids 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 48 50 0 0 0 0 0 0 0 0999 V2000 1.6930 -3.4647 -0.2005 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0130 -2.2298 0.2194 N 0 0 0 0 0 0 0 0 0 0 0 0 1.2428 -1.7175 1.5244 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7076 -1.4068 1.7904 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2657 -0.3954 0.8708 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8837 -0.7655 -0.3009 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4032 0.2077 -1.1648 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3244 1.5511 -0.8932 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6963 1.9182 0.2973 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1912 0.9521 1.1353 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8332 2.5247 -1.7374 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4078 -0.5480 1.8202 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4287 0.0247 2.9677 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4884 0.0446 0.8630 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.7189 1.4650 1.0176 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0464 -0.7914 -0.1311 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8107 -0.2878 -1.2674 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0428 0.4299 -0.9034 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1668 1.7976 -0.9258 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3545 2.3857 -0.5513 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4368 1.6415 -0.1506 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2887 0.2843 -0.1376 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1384 -0.3333 -0.4976 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6343 2.2394 0.2267 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1417 -1.5806 -0.6792 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3138 -1.6334 -1.8998 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9250 -4.2654 -0.3608 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2142 -3.3303 -1.1545 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3539 -3.8292 0.5990 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9838 -2.5702 2.2334 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7486 -0.9948 2.8404 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3038 -2.3415 1.8246 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9927 -1.8009 -0.5900 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8873 -0.0931 -2.0840 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6401 2.9733 0.5006 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7143 1.2684 2.0427 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5461 3.4863 -1.6050 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5264 2.0356 0.1128 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7323 1.5798 1.4373 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0553 1.9104 1.8134 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6673 -1.5813 0.4471 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1468 0.4341 -1.8390 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0854 -1.1080 -2.0063 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3565 2.4496 -1.2446 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4921 3.4759 -0.5555 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1327 -0.3356 0.1765 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0215 -1.4185 -0.4867 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5125 1.7432 0.2060 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 8 11 1 0 3 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 14 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 21 24 1 0 16 25 1 0 25 26 2 0 25 2 1 0 10 5 1 0 23 18 1 0 1 27 1 0 1 28 1 0 1 29 1 0 3 30 1 1 4 31 1 0 4 32 1 0 6 33 1 0 7 34 1 0 9 35 1 0 10 36 1 0 11 37 1 0 15 38 1 0 15 39 1 0 15 40 1 0 16 41 1 1 17 42 1 0 17 43 1 0 19 44 1 0 20 45 1 0 22 46 1 0 23 47 1 0 24 48 1 0 M END

Standard InCHIKey	LVVOUDOWZDIZFR-ROUUACIJSA-N
Standard InCHI	InChI=1S/C20H22N2O4/c1-21-17(11-13-3-7-15(23)8-4-13)20(26)22(2)18(19(21)25)12-14-5-9-16(24)10-6-14/h3-10,17-18,23-24H,11-12H2,1-2H3/t17-,18-/m0/s1
SMILES	CN1[C@@H](Cc2ccc(cc2)O)C(=O)N(C)[C@@H](Cc2ccc(cc2)O)C1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	354.16	Volume:	364.87 ? Van der Waals volume.
Dense:	0.971	LogP:	1.716 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.001 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.26 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	20.0
TPSA:	81.08 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.873	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.054	Fsp³:	0.3
MCE-18:	59.923 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.183	Fluc inhibitor:	0.277 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.03 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.237 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.056	Promiscuous compounds:	0.019

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.753	MDCK Permeability:	-4.761
Pgp-inhibitor:	0.428	Pgp-substrate:	0.903
PAMPA:	0.293 ? 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):	0.016
20% Bioavailability (F20%):	0.99	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.012	MRP1:	0.661
Plasma Protein Binding (PPB):	79.961%	Volume Distribution (VD):	-0.586
Fu:	17.172% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.931	BCRP inhibitor:	0.051
BSEP inhibitor:	0.937

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.031
CYP2C19-inhibitor:	0.433	CYP2C19-substrate:	0.204
CYP2C9-inhibitor:	0.686	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.839	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.996	CYP3A4-substrate:	0.986
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.191
HLM stability:	0.001 ? 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):

10.038

Half-life (T1/2):

1.077

ADMET: Toxicity

hERG Blockers:	0.291	hERG Blockers (10um):	0.419
Human Hepatotoxicity (H-HT):	0.848	Drug-induced Liver Injury (DILI):	0.61
AMES Toxicity:	0.175	Rat Oral Acute Toxicity:	0.695
Maximum Recommended Daily Dose:	0.964	Skin Sensitization:	0.715
Carcinogencity:	0.37	Eye Corrosion:	0.0
Eye Irritation:	0.24	Respiratory Toxicity:	0.908
Drug-induced Neurotoxicity:	0.996	Ototoxicity:	0.443
Hematotoxicity:	0.456	Drug-induced Nephrotoxicity:	0.76
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.271
A549 Cytotoxicity:	0.593	Hek293 Cytotoxicity:	0.972
BCF:	1.153 ? 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:	3.604 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.369 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.053 ? 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
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	DOI[10.1016/j.biotechadv.2015.06.003]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11551769]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[1593278]
NPO3333	Aglaia gigantea	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17880174]
NPO1526	Ratibida latipalearis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1800631]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18232659]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[21693706]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[21939253]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[22101040]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[25730866]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[5447649]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[809439]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3333	Aglaia gigantea	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9227	Xylaria berteri	Species	Xylariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7883	Albugo candida	Species	Albuginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1937	Andropogon nardus	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7365	Clibadium pentaneuron	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12481	Croton californicus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9603	Croton sparsiflorus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18350	Culcitium canescens	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3202	Nolina erumpens	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12535	Solanum toxicarium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24849	Rhinella paracnemis	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1526	Ratibida latipalearis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9937	Piptolepis leptospermoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8416	Picrorhiza kurrooa	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3900	Phellinus xeranticus	Species	Hymenochaetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8547	Petasites niveus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6787	Neoalsomitra integrifolia	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9320	Weddellina squamulosa	Species	Podostemaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12309	Malva crispa	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11355	Homarus americanus	Species	Nephropidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10867	Graphis elongata	Species	Aclididae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO729	Espeletia marcana	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9020	Eriostemon fitzgeraldii	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2805	Distolasterias nipon	Species	Asteriidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5219	Dendrobium rotundatum	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8416	Picrorhiza kurrooa	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[TCMID]
NPO9603	Croton sparsiflorus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8416	Picrorhiza kurrooa	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9603	Croton sparsiflorus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8416	Picrorhiza kurrooa	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO9020	Eriostemon fitzgeraldii	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8547	Petasites niveus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7365	Clibadium pentaneuron	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3900	Phellinus xeranticus	Species	Hymenochaetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7883	Albugo candida	Species	Albuginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24849	Rhinella paracnemis	Species	Bufonidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2805	Distolasterias nipon	Species	Asteriidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO729	Espeletia marcana	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5219	Dendrobium rotundatum	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6787	Neoalsomitra integrifolia	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24652	Toxicodendron succedaneum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8416	Picrorhiza kurrooa	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9603	Croton sparsiflorus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10867	Graphis elongata	Species	Aclididae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11355	Homarus americanus	Species	Nephropidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12481	Croton californicus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12309	Malva crispa	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12535	Solanum toxicarium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3202	Nolina erumpens	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9227	Xylaria berteri	Species	Xylariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1937	Andropogon nardus	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3333	Aglaia gigantea	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9320	Weddellina squamulosa	Species	Podostemaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18350	Culcitium canescens	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9937	Piptolepis leptospermoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1526	Ratibida latipalearis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6232	Streptomyces griseus	Species	Streptomycetaceae	Bacteria	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	2
Inhibition	1

Activity Type	# Activity
Individual protein	2
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3579	Individual protein	Calpain 1	Homo sapiens	IC50	=	800.0	nM	PMID[11551769]
NPT3579	Individual protein	Calpain 1	Homo sapiens	Inhibition	=	0.0	%	PMID[15896956]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	IC50	=	800.0	nM	PMID[15896956]

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 NPC257390 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	17989
0.1-0.2	26961
0.2-0.3	4350
0.3-0.4	508
0.4-0.5	43
0.5-0.6	4
0.6-0.7	3
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	Natural Product ID
0.6944	Remote Similarity	NPC109580
0.6364	Remote Similarity	NPC473418
0.6129	Remote Similarity	NPC258219
0.5758	Remote Similarity	NPC280869
0.575	Remote Similarity	NPC251439
0.5278	Remote Similarity	NPC260000
0.5161	Remote Similarity	NPC197783

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC257390 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3451
0.1-0.2	5274
0.2-0.3	380
0.3-0.4	39
0.4-0.5	6
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