NPASS Compound

Natural Product: NPC165106

Natural Product ID	NPC165106
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Terameprocol
IUPAC Name	4-[(2S,3R)-4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-1,2-dimethoxybenzene
Synonyms	EM-1421; Terameprocol
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL90983
PubChem CID	476861
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001969] Dibenzylbutane lignans

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 56 57 0 0 0 0 0 0 0 0999 V2000 -2.6233 4.2285 -0.2586 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6095 3.3777 -0.8128 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4170 2.0699 -1.1770 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1732 1.4526 -1.0216 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9779 0.1457 -1.3852 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0769 -0.5349 -1.9154 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3069 0.0785 -2.0681 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4824 1.3835 -1.6997 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7066 2.0213 -1.8431 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7967 1.3139 -2.3811 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7179 -0.6038 -1.2654 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5671 -1.3724 0.0195 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5692 -0.5430 1.2424 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4876 0.4593 1.4388 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8756 -0.0081 1.5026 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4033 -0.4322 2.6988 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7141 -0.8474 2.7238 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5065 -0.8512 1.5984 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0030 -0.4318 0.3896 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6657 -0.0136 0.3892 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7892 -0.4334 -0.7380 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3123 -0.0130 -2.0011 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8435 -1.2759 1.6281 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3620 -1.7127 2.8877 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7844 -1.4590 2.4302 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5496 -2.3804 -0.0493 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5015 4.1132 0.8275 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8761 5.2931 -0.4491 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6198 4.0706 -0.7207 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3836 2.0388 -0.6146 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9722 -1.5624 -2.2151 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1565 -0.4581 -2.4816 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4521 0.8448 -3.3495 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6441 2.0041 -2.6250 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1590 0.4952 -1.7338 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6754 -1.3445 -2.1039 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1254 0.0988 -1.3919 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5243 -1.9923 0.0831 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5430 0.0491 1.1975 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3972 1.2599 0.6820 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2922 0.9938 2.4183 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8061 -0.4451 3.6215 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1619 -1.1915 3.6649 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3099 0.3193 -0.5994 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9886 -0.3476 -2.8245 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3028 -0.3553 -2.2434 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3155 1.1028 -2.0559 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1928 -0.9683 3.6875 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3979 -2.0415 2.8027 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7688 -2.6252 3.1834 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0217 -0.8132 3.3054 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0155 -2.1707 2.6124 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7143 -2.0338 2.2217 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1175 -3.3813 -0.2208 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0945 -2.3859 0.9034 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2538 -2.1850 -0.8809 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 5 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 1 0 18 23 1 0 23 24 1 0 13 25 1 0 12 26 1 0 8 3 1 0 20 15 1 0 1 27 1 0 1 28 1 0 1 29 1 0 4 30 1 0 6 31 1 0 7 32 1 0 10 33 1 0 10 34 1 0 10 35 1 0 11 36 1 0 11 37 1 0 12 38 1 1 13 39 1 6 14 40 1 0 14 41 1 0 16 42 1 0 17 43 1 0 20 44 1 0 22 45 1 0 22 46 1 0 22 47 1 0 24 48 1 0 24 49 1 0 24 50 1 0 25 51 1 0 25 52 1 0 25 53 1 0 26 54 1 0 26 55 1 0 26 56 1 0 M END

Standard InCHIKey	ORQFDHFZSMXRLM-IYBDPMFKSA-N
Standard InCHI	InChI=1S/C22H30O4/c1-15(11-17-7-9-19(23-3)21(13-17)25-5)16(2)12-18-8-10-20(24-4)22(14-18)26-6/h7-10,13-16H,11-12H2,1-6H3/t15-,16+
SMILES	COc1cc(ccc1OC)C[C@H]([C@H](Cc1ccc(c(c1)OC)OC)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	358.21	Volume:	391.297 ? Van der Waals volume.
Dense:	0.915	LogP:	3.059 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.046 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.95 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	12.0
TPSA:	36.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.646	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.626	Fsp³:	0.455
MCE-18:	28.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.324	Fluc inhibitor:	0.31 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.084 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.658	Promiscuous compounds:	0.114

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.556	MDCK Permeability:	-4.572
Pgp-inhibitor:	0.729	Pgp-substrate:	0.148
PAMPA:	0.007 ? 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):	0.001
20% Bioavailability (F20%):	0.187	30% Bioavailability (F30%):	0.84
50% Bioavailability (F50%):	0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.432
Plasma Protein Binding (PPB):	89.628%	Volume Distribution (VD):	0.143
Fu:	8.936% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.66
OATP1B3 inhibitor:	0.874	BCRP inhibitor:	0.836
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.987	CYP1A2-substrate:	0.785
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.5	CYP2C9-substrate:	0.998
CYP2D6-inhibitor:	0.323	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.959	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):

8.385

Half-life (T1/2):

1.311

ADMET: Toxicity

hERG Blockers:	0.46	hERG Blockers (10um):	0.831
Human Hepatotoxicity (H-HT):	0.596	Drug-induced Liver Injury (DILI):	0.438
AMES Toxicity:	0.258	Rat Oral Acute Toxicity:	0.12
Maximum Recommended Daily Dose:	0.051	Skin Sensitization:	0.813
Carcinogencity:	0.305	Eye Corrosion:	0.966
Eye Irritation:	0.997	Respiratory Toxicity:	0.08
Drug-induced Neurotoxicity:	0.452	Ototoxicity:	0.578
Hematotoxicity:	0.538	Drug-induced Nephrotoxicity:	0.647
Genotoxicity:	0.003	RPMI-8226 Immunitoxicity:	0.17
A549 Cytotoxicity:	0.197	Hek293 Cytotoxicity:	0.254
BCF:	2.751 ? 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:	4.483 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.329 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.143 ? 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
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1002/cjoc.20010190319]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1016/j.tet.2008.10.079]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	PMID[11395273]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	PMID[18536373]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	aerial parts	Erlang Mountain area of Sichuan Province, China	2007-SEP	PMID[19413342]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20681569]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7374	Seseli montanum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7374	Seseli montanum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11167	Prunus ssiori	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9834	Veronica austriaca	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6903	Lecanora straminea	Species	Lecanoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7128	Cynthia savignyi	n.a.	n.a.	n.a.	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
Inhibition	32
IC50	33
EC50	1
Activity	21
GI50	6
-logMIC	3
MIC	6
HC10	1
Ratio CC50/EC50	1
CC50	2
Change	2
ED50	1

Activity Type	# Activity
Cell line	66
Organism	33
Single protein	2
Individual protein	2
Non-molecular	5
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.57	%	DOI[10.6019/CHEMBL4495564]
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	14.64	%	DOI[10.6019/CHEMBL4495564]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-2.57	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-12.68	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	11700.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	4400.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	8240.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	5970.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	6480.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	6980.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	9910.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	8820.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	4470.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	4180.0	nM	PMID[9685239]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	11080.0	nM	PMID[9685239]
NPT3886	Cell line	COS-1	Chlorocebus aethiops	Inhibition	=	18.5	%	PMID[9685238]
NPT3886	Cell line	COS-1	Chlorocebus aethiops	Inhibition	=	25.3	%	PMID[9685238]
NPT3886	Cell line	COS-1	Chlorocebus aethiops	Inhibition	=	45.0	%	PMID[9685238]
NPT3886	Cell line	COS-1	Chlorocebus aethiops	Inhibition	=	61.0	%	PMID[9685238]
NPT3886	Cell line	COS-1	Chlorocebus aethiops	Inhibition	=	70.0	%	PMID[9685238]
NPT3886	Cell line	COS-1	Chlorocebus aethiops	Inhibition	=	78.7	%	PMID[9685238]
NPT3886	Cell line	COS-1	Chlorocebus aethiops	Inhibition	=	90.3	%	PMID[9685238]
NPT3886	Cell line	COS-1	Chlorocebus aethiops	IC50	=	11090.0	nM	PMID[9685238]
NPT1083	Cell line	A-375	Homo sapiens	IC50	=	16600.0	nM	PMID[19615898]
NPT1083	Cell line	A-375	Homo sapiens	Inhibition	=	23.0	%	PMID[19615898]
NPT1083	Cell line	A-375	Homo sapiens	Inhibition	=	31.0	%	PMID[19615898]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	42400.0	nM	PMID[19615898]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	44500.0	nM	PMID[19615898]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	61500.0	nM	PMID[19615898]
NPT1083	Cell line	A-375	Homo sapiens	Inhibition	=	70.0	%	PMID[19615898]
NPT1083	Cell line	A-375	Homo sapiens	IC50	=	2500.0	nM	PMID[19615898]
NPT858	Cell line	LNCaP	Homo sapiens	IC50	<=	10000.0	nM	PMID[21123067]
NPT139	Cell line	HT-29	Homo sapiens	IC50	<=	10000.0	nM	PMID[21123067]
NPT83	Cell line	MCF7	Homo sapiens	IC50	<=	10000.0	nM	PMID[21123067]
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	IC50	<=	10000.0	nM	PMID[21123067]
NPT111	Cell line	K562	Homo sapiens	Activity	=	170.7	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	168.0	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	331.5	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	615.3	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	477.8	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	597.2	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	IC50	=	5.87	ug.mL-1	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Inhibition	=	79.64	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Inhibition	=	52.93	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Inhibition	=	33.16	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Inhibition	=	5.06	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Inhibition	=	-5.88	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Inhibition	=	-12.79	%	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	8.527	10'-5/min	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	1.971	10'-4/min	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	2.799	10'-4/min	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	3.976	10'-4/min	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	4.434	10'-4/min	PMID[23434529]
NPT111	Cell line	K562	Homo sapiens	Activity	=	4.724	10'-4/min	PMID[23434529]
NPT1125	Cell line	T98G	Homo sapiens	GI50	>	50000.0	nM	PMID[24080463]
NPT165	Cell line	HeLa	Homo sapiens	GI50	>	50000.0	nM	PMID[24080463]
NPT396	Cell line	T47D	Homo sapiens	GI50	=	5360.0	nM	PMID[24080463]
NPT401	Cell line	786-0	Homo sapiens	GI50	=	4540.0	nM	PMID[24080463]
NPT1081	Cell line	BXPC-3	Homo sapiens	GI50	=	17100.0	nM	PMID[24080463]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	44500.0	nM	PMID[38092421]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	42400.0	nM	PMID[38092421]
NPT1083	Cell line	A-375	Homo sapiens	IC50	=	16600.0	nM	PMID[38092421]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	61500.0	nM	PMID[38092421]
NPT941	Cell line	HaCaT	Homo sapiens	IC50	=	85000.0	nM	PMID[38092421]
NPT1452	Cell line	C8166	Homo sapiens	CC50	=	28800.0	nM	PMID[19413342]
NPT71	Cell line	HEK293	Homo sapiens	CC50	>	20000.0	nM	DOI[10.6019/CHEMBL4513161]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-5.2	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.64	%	DOI[10.6019/CHEMBL4495565]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.0	%	DOI[10.6019/CHEMBL4495565]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	5000.0	nM	PMID[19615898]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	66.0	%	PMID[19615898]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	94.0	%	PMID[19615898]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	<=	10000.0	nM	PMID[21123067]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	>	50000.0	nM	PMID[24080463]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	-logMIC	=	4.35	n.a.	PMID[28844400]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	-logMIC	=	4.95	n.a.	PMID[28844400]
NPT20	Organism	Candida albicans	Candida albicans	MIC	>	20000.0	nM	DOI[10.6019/CHEMBL4513161]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	MIC	>	20000.0	nM	DOI[10.6019/CHEMBL4513161]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	14800.0	nM	PMID[19413342]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	IC50	=	330.0	ug.mL-1	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Inhibition	=	67.72	%	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Inhibition	=	44.7	%	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Inhibition	=	27.31	%	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Inhibition	=	11.51	%	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Inhibition	=	4.06	%	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Inhibition	=	8.13	%	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Inhibition	=	9.48	%	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Activity	=	0.00143	/min	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Activity	=	0.00245	/min	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Activity	=	0.00322	/min	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Activity	=	0.00392	/min	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Activity	=	0.00425	/min	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Activity	=	0.00407	/min	PMID[23434529]
NPT765	Organism	Schizosaccharomyces pombe	Schizosaccharomyces pombe	Activity	=	0.00401	/min	PMID[23434529]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	20000.0	nM	DOI[10.6019/CHEMBL4513161]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	>	20000.0	nM	DOI[10.6019/CHEMBL4513161]
NPT20950	Cell line	Erythrocyte	n.a.	HC10	>	20.0	uM	DOI[10.6019/CHEMBL4513161]
NPT747	Organism	Acinetobacter baumannii	Acinetobacter baumannii	MIC	>	20000.0	nM	DOI[10.6019/CHEMBL4513161]
NPT2	Others	Unspecified	n.a.	Ratio CC50/EC50	=	2.0	n.a.	PMID[19413342]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Change	=	-2.66	%	PMID[9685239]
NPT32	Organism	Mus musculus	Mus musculus	Change	=	-2.8	%	PMID[9685239]
NPT32	Organism	Mus musculus	Mus musculus	ED50	=	1000.0	mg.kg-1	PMID[19615898]

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference
Mus musculus	n.a.	Cmax	=	2970.88	nM	PMID[38092421]
Mus musculus	Plasma	F	=	88.29	%	PMID[38092421]
Mus musculus	Plasma	AUC	=	2984.54	ng.hr.mL-1	PMID[38092421]
Mus musculus	n.a.	Cmax	=	1231.59	nM	PMID[38092421]

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 NPC165106 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	23336
0.1-0.2	22443
0.2-0.3	3516
0.3-0.4	419
0.4-0.5	102
0.5-0.6	24
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.871	High Similarity	NPC477886
0.7941	Intermediate Similarity	NPC344161
0.7105	Intermediate Similarity	NPC227217
0.7105	Intermediate Similarity	NPC117780
0.6765	Remote Similarity	NPC80241
0.6765	Remote Similarity	NPC301641
0.6765	Remote Similarity	NPC485483
0.6571	Remote Similarity	NPC81067
0.6571	Remote Similarity	NPC602945
0.625	Remote Similarity	NPC292792
0.5882	Remote Similarity	NPC254625
0.5882	Remote Similarity	NPC120075
0.5556	Remote Similarity	NPC274356
0.5556	Remote Similarity	NPC475961
0.5556	Remote Similarity	NPC137685
0.5556	Remote Similarity	NPC101748
0.5532	Remote Similarity	NPC474017
0.5476	Remote Similarity	NPC223807
0.5405	Remote Similarity	NPC303522
0.5405	Remote Similarity	NPC298486
0.5349	Remote Similarity	NPC249788
0.5263	Remote Similarity	NPC165133
0.5263	Remote Similarity	NPC242885
0.5263	Remote Similarity	NPC95614
0.5263	Remote Similarity	NPC76451
0.5263	Remote Similarity	NPC232316
0.5263	Remote Similarity	NPC609746
0.5227	Remote Similarity	NPC482890
0.5227	Remote Similarity	NPC607444
0.5152	Remote Similarity	NPC258425
0.5143	Remote Similarity	NPC474691
0.5128	Remote Similarity	NPC251855
0.5128	Remote Similarity	NPC205502
0.5111	Remote Similarity	NPC485480

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC165106 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3629
0.1-0.2	5023
0.2-0.3	444
0.3-0.4	48
0.4-0.5	5
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD5283	Phase 2

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