NPASS Compound

Natural Product: NPC475479

Natural Product ID	NPC475479
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ULYPVLZRRZENPT-WDYNHAJCSA-N
IUPAC Name	n.a.
Synonyms	(+)-2-Norobaberine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL506363
PubChem CID	21582958
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds

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 85 91 0 0 0 0 0 0 0 0999 V2000 -3.1203 3.5468 -2.9825 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5443 2.7792 -1.8145 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.2186 3.7215 -0.9414 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4389 3.2124 0.4474 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9009 1.8677 0.7015 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4810 1.1563 1.7519 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0050 -0.1144 1.9785 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9885 -0.6408 1.1780 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4134 0.0518 0.1445 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9068 1.3482 -0.0762 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3563 2.2276 -1.1615 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4909 3.3042 -0.6019 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0432 3.0614 -0.6306 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6622 2.8649 0.5616 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0021 2.6511 0.5346 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6848 2.6237 -0.6547 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9937 2.8170 -1.8214 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6346 3.0360 -1.8304 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0769 2.3940 -0.6512 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4916 1.3575 0.2123 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7366 1.3953 0.7656 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1047 0.3474 1.6221 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1921 -0.6576 1.8563 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9223 -0.7074 1.2990 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6034 0.3339 0.4678 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9567 -1.8018 1.5980 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6805 -2.7238 0.4806 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3611 -2.5719 -0.1811 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5308 -1.4911 -0.0637 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6485 -1.4519 -0.7780 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0223 -2.4902 -1.6168 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1938 -3.5741 -1.7327 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9935 -3.6298 -1.0267 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8202 -4.8354 -1.2070 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9265 -4.9924 -0.2179 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7259 -4.1201 0.9248 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2231 -2.3675 -2.2933 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6085 -3.4327 -3.1534 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4465 -0.3801 -0.6611 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6142 2.4008 0.5153 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9033 2.5163 1.0436 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5565 -1.9193 1.4571 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2289 -3.0103 0.8636 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5141 -0.9054 2.9986 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5430 -0.3665 3.8045 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0391 4.6287 -2.7374 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1969 3.1431 -3.4295 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9630 3.4751 -3.7091 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7101 4.6830 -1.0187 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2369 3.8775 -1.4032 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9725 3.9171 1.1606 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5227 3.2008 0.7210 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2649 1.5713 2.3646 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8325 1.6142 -1.8898 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7183 4.2976 -1.0915 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7675 3.4697 0.4689 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1208 2.8884 1.4748 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5404 2.5009 1.4473 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5075 2.8016 -2.7746 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1125 3.1839 -2.7387 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0888 0.3482 2.0779 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4527 -1.4933 2.5249 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6592 0.3722 -0.0135 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0398 -1.2957 2.0201 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3878 -2.3468 2.4796 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5047 -2.6471 -0.2935 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7411 -0.6544 0.5899 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4940 -4.3986 -2.3992 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1993 -5.7720 -1.1932 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2748 -4.8417 -2.2352 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9305 -4.8194 -0.6801 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9437 -6.0401 0.1914 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7770 -4.3325 1.3046 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5276 -3.1145 -3.6953 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8772 -4.2791 -2.4615 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8042 -3.7548 -3.8201 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3878 1.5064 1.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9538 2.8715 2.0784 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5235 3.1446 0.3500 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5542 -3.7872 0.4733 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8827 -2.6544 0.0434 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9299 -3.4947 1.6049 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9925 -1.1238 4.4746 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3814 0.0451 3.1748 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2019 0.4787 4.4354 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 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 16 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 1 0 35 36 1 0 31 37 1 0 37 38 1 0 30 39 1 0 21 40 1 0 40 41 1 0 8 42 1 0 42 43 1 0 7 44 1 0 44 45 1 0 11 2 1 0 10 5 1 0 39 9 1 0 18 13 1 0 25 20 1 0 36 27 1 0 33 28 1 0 1 46 1 0 1 47 1 0 1 48 1 0 3 49 1 0 3 50 1 0 4 51 1 0 4 52 1 0 6 53 1 0 11 54 1 0 12 55 1 0 12 56 1 0 14 57 1 0 15 58 1 0 17 59 1 0 18 60 1 0 22 61 1 0 23 62 1 0 25 63 1 0 26 64 1 0 26 65 1 0 27 66 1 0 29 67 1 0 32 68 1 0 34 69 1 0 34 70 1 0 35 71 1 0 35 72 1 0 36 73 1 0 38 74 1 0 38 75 1 0 38 76 1 0 41 77 1 0 41 78 1 0 41 79 1 0 43 80 1 0 43 81 1 0 43 82 1 0 45 83 1 0 45 84 1 0 45 85 1 0 M END

Standard InCHIKey	ULYPVLZRRZENPT-WDYNHAJCSA-N
Standard InCHI	InChI=1S/C37H40N2O6/c1-39-15-13-25-20-34(42-4)36(43-5)37-35(25)29(39)17-22-6-9-26(10-7-22)44-32-18-23(8-11-30(32)40-2)16-28-27-21-33(45-37)31(41-3)19-24(27)12-14-38-28/h6-11,18-21,28-29,38H,12-17H2,1-5H3/t28-,29+/m1/s1
SMILES	CN1CCC2=CC(=C(C3=C2C1CC4=CC=C(C=C4)OC5=C(C=CC(=C5)CC6C7=CC(=C(C=C7CCN6)OC)O3)OC)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	608.29	Volume:	631.71 ? Van der Waals volume.
Dense:	0.963	LogP:	3.158 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.119 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.239 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	42.0
TPSA:	70.65 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	8.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.271	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.758	Fsp³:	0.351
MCE-18:	126.16 ? 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:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.996	Fluc inhibitor:	0.017 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.581 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.855 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.143

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.877	MDCK Permeability:	-4.765
Pgp-inhibitor:	0.316	Pgp-substrate:	0.784
PAMPA:	0.034 ? 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%):	0.017	30% Bioavailability (F30%):	0.009
50% Bioavailability (F50%):	0.859

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.842	MRP1:	0.981
Plasma Protein Binding (PPB):	70.013%	Volume Distribution (VD):	0.198
Fu:	30.974% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.306
OATP1B3 inhibitor:	0.985	BCRP inhibitor:	0.625
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.967	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.987	CYP2C8-inhibitor:	0.0
HLM stability:	0.044 ? 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):

7.754

Half-life (T1/2):

2.175

ADMET: Toxicity

hERG Blockers:	0.921	hERG Blockers (10um):	0.864
Human Hepatotoxicity (H-HT):	0.57	Drug-induced Liver Injury (DILI):	0.044
AMES Toxicity:	0.707	Rat Oral Acute Toxicity:	0.715
Maximum Recommended Daily Dose:	0.898	Skin Sensitization:	0.929
Carcinogencity:	0.556	Eye Corrosion:	0.0
Eye Irritation:	0.002	Respiratory Toxicity:	0.969
Drug-induced Neurotoxicity:	0.864	Ototoxicity:	0.884
Hematotoxicity:	0.077	Drug-induced Nephrotoxicity:	0.408
Genotoxicity:	0.089	RPMI-8226 Immunitoxicity:	0.079
A549 Cytotoxicity:	0.147	Hek293 Cytotoxicity:	0.651
BCF:	1.914 ? 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:	4.226 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.85 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.982 ? 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
NPO26964	Stephania erecta	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8450319]
NPO26964	Stephania erecta	Species	Menispermaceae	Eukaryota	tubers	n.a.	n.a.	PMID[8450319]
NPO26964	Stephania erecta	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26964	Stephania erecta	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26964	Stephania erecta	Species	Menispermaceae	Eukaryota	tubers	n.a.	n.a.	Database[PMID; Title]
NPO32960	stephania pierrii	Species	Menispermaceae	Eukaryota	tubers	n.a.	n.a.	Database[PMID; Title]
NPO26964	Stephania erecta	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26964	Stephania erecta	Species	Menispermaceae	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
ED50	10
Ratio ED50	22
IC50	2

Activity Type	# Activity
Cell line	8
Organism	4
Others	22

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
NPT453	Cell line	HT-1080	Homo sapiens	ED50	=	7.4	ug ml-1	PMID[19721074]
NPT147	Cell line	SK-MEL-2	Homo sapiens	ED50	=	14.5	ug ml-1	DOI[10.6019/CHEMBL1201861]
NPT91	Cell line	KB	Homo sapiens	ED50	=	6.0	ug ml-1	PMID[11975502]
NPT168	Cell line	P388	Mus musculus	ED50	=	3.5	ug ml-1	PMID[16643039]
NPT762	Cell line	A-431	Homo sapiens	ED50	=	6.1	ug ml-1	PMID[17190448]
NPT858	Cell line	LNCaP	Homo sapiens	ED50	=	3.7	ug ml-1	DrugMatrix in vivo data: Biochemistry
NPT133	Cell line	ZR-75-1	Homo sapiens	ED50	=	1.2	ug ml-1	PMID[19029333]
NPT91	Cell line	KB	Homo sapiens	ED50	=	9900.0	nM	PMID[22871217]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	45.9	ng/ml	DrugMatrix in vivo data: Pathology
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	93.7	ng/ml	PMID[19428246]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	75.0	nM	PMID[22871217]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	154.0	nM	PMID[21130541]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	70.0	n.a.	PMID[10924160]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	34.0	n.a.	PMID[17844994]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	161.0	n.a.	PMID[26241103]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	79.0	n.a.	PMID[12662094]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	192.0	n.a.	PMID[26686929]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	94.0	n.a.	DrugMatrix in vivo data: Pathology
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	316.0	n.a.	PMID[9392880]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	155.0	n.a.	PMID[17477572]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	120.0	n.a.	PMID[19651905]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	17.4	n.a.	PMID[12398531]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	131.0	n.a.	PMID[19926364]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	64.0	n.a.	PMID[15387655]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	44.0	n.a.	DOI[10.1007/s00044-011-9605-5]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	21.0	n.a.	PMID[17844994]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	76.0	n.a.	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	37.0	n.a.	DOI[10.1016/j.cropro.2012.04.001]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	133.0	n.a.	PMID[20627740]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	65.0	n.a.	PMID[9514009]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	81.0	n.a.	PMID[15387655]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	40.0	n.a.	PMID[23398362]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	41.0	n.a.	PMID[20805391]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	20.0	n.a.	PMID[8450319]

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 NPC475479 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	36466
0.1-0.2	12829
0.2-0.3	365
0.3-0.4	91
0.4-0.5	43
0.5-0.6	34
0.6-0.7	13
0.7-0.8	1
0.8-0.85	2
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9459	High Similarity	NPC323537
0.8861	High Similarity	NPC281581
0.8171	Intermediate Similarity	NPC11296
0.8171	Intermediate Similarity	NPC274661
0.7778	Intermediate Similarity	NPC243454
0.7375	Intermediate Similarity	NPC475393
0.7143	Intermediate Similarity	NPC76682
0.7143	Intermediate Similarity	NPC10908
0.7143	Intermediate Similarity	NPC63646
0.7143	Intermediate Similarity	NPC317145
0.7143	Intermediate Similarity	NPC198498
0.7143	Intermediate Similarity	NPC115284
0.7111	Intermediate Similarity	NPC175890
0.7051	Intermediate Similarity	NPC276890
0.7	Intermediate Similarity	NPC191132
0.6556	Remote Similarity	NPC82457
0.6517	Remote Similarity	NPC239584
0.6438	Remote Similarity	NPC317439
0.6341	Remote Similarity	NPC227060
0.631	Remote Similarity	NPC73492
0.631	Remote Similarity	NPC299990
0.631	Remote Similarity	NPC480587
0.6277	Remote Similarity	NPC48490
0.6071	Remote Similarity	NPC12424
0.6071	Remote Similarity	NPC129518
0.6071	Remote Similarity	NPC251580
0.6024	Remote Similarity	NPC41376
0.6	Remote Similarity	NPC603853
0.596	Remote Similarity	NPC256124
0.5909	Remote Similarity	NPC185639
0.5909	Remote Similarity	NPC251735
0.5909	Remote Similarity	NPC49075
0.5909	Remote Similarity	NPC599951
0.5795	Remote Similarity	NPC311973
0.5769	Remote Similarity	NPC247639
0.5769	Remote Similarity	NPC25084
0.5761	Remote Similarity	NPC485712
0.5747	Remote Similarity	NPC290582
0.5747	Remote Similarity	NPC217748
0.5747	Remote Similarity	NPC182052
0.5747	Remote Similarity	NPC271013
0.5747	Remote Similarity	NPC42663
0.5747	Remote Similarity	NPC15414
0.573	Remote Similarity	NPC116465
0.573	Remote Similarity	NPC223690
0.573	Remote Similarity	NPC9532
0.5682	Remote Similarity	NPC279228
0.5638	Remote Similarity	NPC10871
0.5495	Remote Similarity	NPC229373
0.5444	Remote Similarity	NPC239824
0.5417	Remote Similarity	NPC480590
0.5385	Remote Similarity	NPC254441
0.5357	Remote Similarity	NPC475215
0.5306	Remote Similarity	NPC485711
0.53	Remote Similarity	NPC60295
0.5263	Remote Similarity	NPC24260
0.5263	Remote Similarity	NPC249996
0.5258	Remote Similarity	NPC480586
0.5213	Remote Similarity	NPC16357
0.5213	Remote Similarity	NPC302245
0.5213	Remote Similarity	NPC195538
0.5056	Remote Similarity	NPC603603

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475479 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5285
0.1-0.2	3783
0.2-0.3	70
0.3-0.4	8
0.4-0.5	1
0.5-0.6	1
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
0.7143	Intermediate Similarity	NPD8099	Discontinued
0.6585	Remote Similarity	NPD8156	Discontinued
0.593	Remote Similarity	NPD8095	Phase 1

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