NPASS Compound

Natural Product: NPC11296

Natural Product ID	NPC11296
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	REKCBEFSIKOPTD-IZLXSDGUSA-N
IUPAC Name	n.a.
Synonyms	(+)-Daphandrine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL510612
PubChem CID	442214
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 82 88 0 0 0 0 0 0 0 0999 V2000 -2.4601 4.0888 -2.6937 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0924 2.8627 -2.1111 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9869 2.6958 -1.2863 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1490 3.7380 -0.9689 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9200 3.4954 -0.1498 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8721 4.5644 0.2455 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1789 4.4163 1.6981 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3525 3.1008 2.1939 N 0 0 0 0 0 0 0 0 0 0 0 0 2.3394 2.0376 1.2341 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1618 2.2282 0.3544 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3191 1.1966 0.0310 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7608 1.4494 -0.7983 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5728 0.3544 -1.0831 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4360 -0.2036 -0.1525 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9645 -1.4451 -0.2100 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8263 -1.8594 0.8177 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3465 -3.2593 0.6416 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8539 -3.4991 -0.7424 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0709 -2.8184 -1.7632 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.7661 -2.4816 -1.2363 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7383 -2.2263 -2.2588 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3471 -2.3551 -1.8233 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0386 -2.5280 -0.5053 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2792 -2.6474 -0.0983 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2941 -2.5920 -1.0300 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6341 -2.7058 -0.6673 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3170 -1.6199 -0.1075 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7150 -0.3842 -0.0983 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3075 0.7381 0.4288 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6241 2.0521 0.4183 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5668 0.5911 0.9684 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2059 -0.6566 0.9732 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5706 -1.7488 0.4334 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1743 -2.9933 0.4228 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4644 -3.1206 0.9796 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0002 -2.4187 -2.3621 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6666 -2.3011 -2.7462 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8334 -1.6532 -2.1636 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1570 -1.0733 1.8697 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6140 0.1992 1.9264 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7649 0.6074 0.9142 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2462 1.9089 1.0283 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9158 1.0327 2.9674 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7644 0.6846 4.0211 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4070 4.9197 -1.9568 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8626 4.2855 -3.6101 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5271 4.0270 -2.9970 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3405 4.7272 -1.3645 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2870 5.5276 0.1383 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7666 4.6048 -0.4087 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1557 4.9551 1.8652 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4419 4.9684 2.3295 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1525 2.9873 2.8233 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2894 1.0331 1.7103 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5400 0.2208 0.4433 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1733 -3.3633 1.3715 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5639 -4.0014 0.9432 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9241 -3.1769 -0.7635 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8690 -4.5970 -0.9396 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4447 -3.4096 -0.6715 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9706 -2.9264 -3.1249 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8550 -1.2176 -2.7584 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8229 -2.5734 0.2279 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5483 -2.7841 0.9330 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7316 -0.2913 -0.5253 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3072 2.8436 0.7736 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3698 2.3053 -0.6534 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0989 1.4199 1.4009 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1958 -0.7459 1.4029 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4982 -2.6754 1.9825 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8095 -4.1722 0.9958 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1545 -2.5939 0.2610 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7757 -2.3731 -3.1076 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4545 -2.1672 -3.7835 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2659 -0.9258 -2.7460 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6525 -2.0339 -2.8332 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3666 -1.2129 -1.2902 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8320 -1.4418 2.6428 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9200 2.6570 0.8725 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8762 1.5527 4.7139 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7480 0.3848 3.5848 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4128 -0.1885 4.6058 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 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 2 0 15 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 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 1 0 29 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 1 0 25 36 1 0 36 37 2 0 19 38 1 0 16 39 2 0 39 40 1 0 40 41 2 0 41 42 1 0 40 43 1 0 43 44 1 0 12 3 1 0 41 14 1 0 10 5 2 0 20 15 1 0 37 22 1 0 30 9 1 0 33 27 1 0 1 45 1 0 1 46 1 0 1 47 1 0 4 48 1 0 6 49 1 0 6 50 1 0 7 51 1 0 7 52 1 0 8 53 1 0 9 54 1 1 11 55 1 0 17 56 1 0 17 57 1 0 18 58 1 0 18 59 1 0 20 60 1 1 21 61 1 0 21 62 1 0 23 63 1 0 24 64 1 0 28 65 1 0 30 66 1 0 30 67 1 0 31 68 1 0 32 69 1 0 35 70 1 0 35 71 1 0 35 72 1 0 36 73 1 0 37 74 1 0 38 75 1 0 38 76 1 0 38 77 1 0 39 78 1 0 42 79 1 0 44 80 1 0 44 81 1 0 44 82 1 0 M END

Standard InCHIKey	REKCBEFSIKOPTD-IZLXSDGUSA-N
Standard InCHI	InChI=1S/C36H38N2O6/c1-38-14-12-24-19-33(42-4)35(39)36-34(24)28(38)16-21-5-8-25(9-6-21)43-31-17-22(7-10-29(31)40-2)15-27-26-20-32(44-36)30(41-3)18-23(26)11-13-37-27/h5-10,17-20,27-28,37,39H,11-16H2,1-4H3/t27-,28+/m1/s1
SMILES	COc1cc2CCN[C@H]3c2cc1Oc1c2c(CCN([C@H]2Cc2ccc(Oc4cc(C3)ccc4OC)cc2)C)cc(c1O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	594.27	Volume:	614.414 ? Van der Waals volume.
Dense:	0.967	LogP:	2.812 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.767 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.764 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	42.0
TPSA:	81.65 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	2.0	Rings:	8.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.278	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.776	Fsp³:	0.333
MCE-18:	126.667 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.997	Fluc inhibitor:	0.326 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.628 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.945 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.246

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.201	MDCK Permeability:	-4.862
Pgp-inhibitor:	0.114	Pgp-substrate:	0.947
PAMPA:	0.014 ? 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):	0.002
20% Bioavailability (F20%):	0.321	30% Bioavailability (F30%):	0.328
50% Bioavailability (F50%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.17	MRP1:	0.956
Plasma Protein Binding (PPB):	78.758%	Volume Distribution (VD):	-0.259
Fu:	20.726% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.961
OATP1B3 inhibitor:	0.987	BCRP inhibitor:	0.678
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.997	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.996	CYP3A4-substrate:	0.034
CYP2B6-substrate:	0.738	CYP2C8-inhibitor:	0.005
HLM stability:	0.049 ? 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):

6.082

Half-life (T1/2):

2.704

ADMET: Toxicity

hERG Blockers:	0.816	hERG Blockers (10um):	0.81
Human Hepatotoxicity (H-HT):	0.651	Drug-induced Liver Injury (DILI):	0.058
AMES Toxicity:	0.752	Rat Oral Acute Toxicity:	0.854
Maximum Recommended Daily Dose:	0.971	Skin Sensitization:	0.783
Carcinogencity:	0.417	Eye Corrosion:	0.0
Eye Irritation:	0.024	Respiratory Toxicity:	0.938
Drug-induced Neurotoxicity:	0.885	Ototoxicity:	0.477
Hematotoxicity:	0.075	Drug-induced Nephrotoxicity:	0.504
Genotoxicity:	0.393	RPMI-8226 Immunitoxicity:	0.083
A549 Cytotoxicity:	0.281	Hek293 Cytotoxicity:	0.466
BCF:	1.736 ? 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:	4.373 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.64 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.124 ? 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]
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	9
Ratio ED50	22

Activity Type	# Activity
Cell line	7
Organism	2
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	=	6.9	ug ml-1	PMID[19459645]
NPT147	Cell line	SK-MEL-2	Homo sapiens	ED50	=	13.4	ug ml-1	PMID[17618015]
NPT91	Cell line	KB	Homo sapiens	ED50	=	5.8	ug ml-1	PMID[1791472]
NPT168	Cell line	P388	Mus musculus	ED50	=	2.0	ug ml-1	PMID[24144848]
NPT762	Cell line	A-431	Homo sapiens	ED50	=	8.3	ug ml-1	PMID[23466234]
NPT858	Cell line	LNCaP	Homo sapiens	ED50	=	5.8	ug ml-1	PMID[22071302]
NPT133	Cell line	ZR-75-1	Homo sapiens	ED50	=	1.2	ug ml-1	PMID[19425589]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	63.0	ng/ml	PMID[12880304]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	223.2	ng/ml	PMID[22705001]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	73.0	n.a.	PMID[10560729]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	21.0	n.a.	PMID[19114678]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	110.0	n.a.	PMID[8158160]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	31.0	n.a.	PMID[22036992]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	143.0	n.a.	PMID[22705001]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	40.0	n.a.	PMID[7775984]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	213.0	n.a.	DOI[10.6019/CHEMBL1201861]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	60.0	n.a.	PMID[1517739]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	164.0	n.a.	PMID[8691203]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	46.0	n.a.	PMID[25978520]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	92.0	n.a.	DrugMatrix in vitro pharmacology data
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	26.0	n.a.	PMID[18557621]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	35.0	n.a.	PMID[19591488]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	10.0	n.a.	PMID[19746919]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	32.0	n.a.	PMID[25856683]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	9.0	n.a.	PMID[24893224]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	132.0	n.a.	PMID[9051914]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	37.0	n.a.	PMID[15646539]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	29.0	n.a.	PMID[17432904]
NPT2	Others	Unspecified	n.a.	Ratio ED50	=	8.0	n.a.	PMID[17503850]

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 NPC11296 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	31156
0.1-0.2	17823
0.2-0.3	666
0.3-0.4	90
0.4-0.5	58
0.5-0.6	37
0.6-0.7	14
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC274661
0.8706	High Similarity	NPC175890
0.8171	Intermediate Similarity	NPC475479
0.7907	Intermediate Similarity	NPC82457
0.7738	Intermediate Similarity	NPC323537
0.7701	Intermediate Similarity	NPC281581
0.7317	Intermediate Similarity	NPC290582
0.7317	Intermediate Similarity	NPC217748
0.7317	Intermediate Similarity	NPC182052
0.7317	Intermediate Similarity	NPC271013
0.7317	Intermediate Similarity	NPC42663
0.7317	Intermediate Similarity	NPC15414
0.7024	Intermediate Similarity	NPC279228
0.6941	Remote Similarity	NPC475393
0.6809	Remote Similarity	NPC48490
0.6809	Remote Similarity	NPC191132
0.6742	Remote Similarity	NPC243454
0.641	Remote Similarity	NPC104196
0.6333	Remote Similarity	NPC181796
0.6333	Remote Similarity	NPC54654
0.6333	Remote Similarity	NPC7715
0.6333	Remote Similarity	NPC328155
0.6333	Remote Similarity	NPC222661
0.6333	Remote Similarity	NPC285931
0.6222	Remote Similarity	NPC229373
0.6154	Remote Similarity	NPC290005
0.6	Remote Similarity	NPC239584
0.5952	Remote Similarity	NPC475215
0.5825	Remote Similarity	NPC256124
0.5824	Remote Similarity	NPC311973
0.5747	Remote Similarity	NPC76682
0.5747	Remote Similarity	NPC10908
0.5747	Remote Similarity	NPC63646
0.5747	Remote Similarity	NPC317145
0.5747	Remote Similarity	NPC198498
0.5747	Remote Similarity	NPC115284
0.5682	Remote Similarity	NPC276890
0.5625	Remote Similarity	NPC275680
0.5625	Remote Similarity	NPC22115
0.5618	Remote Similarity	NPC603603
0.5591	Remote Similarity	NPC116465
0.5484	Remote Similarity	NPC239824
0.5435	Remote Similarity	NPC73492
0.5435	Remote Similarity	NPC299990
0.5426	Remote Similarity	NPC254441
0.5422	Remote Similarity	NPC247639
0.5422	Remote Similarity	NPC25084
0.5385	Remote Similarity	NPC12424
0.5385	Remote Similarity	NPC129518
0.5385	Remote Similarity	NPC251580
0.534	Remote Similarity	NPC60295
0.5333	Remote Similarity	NPC41376
0.5326	Remote Similarity	NPC603853
0.5306	Remote Similarity	NPC8836
0.5263	Remote Similarity	NPC185639
0.5263	Remote Similarity	NPC251735
0.5263	Remote Similarity	NPC49075
0.5263	Remote Similarity	NPC599951
0.5158	Remote Similarity	NPC286119
0.5109	Remote Similarity	NPC227060
0.5106	Remote Similarity	NPC480587
0.5104	Remote Similarity	NPC223690
0.5104	Remote Similarity	NPC9532
0.506	Remote Similarity	NPC317439

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC11296 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4816
0.1-0.2	4254
0.2-0.3	68
0.3-0.4	7
0.4-0.5	2
0.5-0.6	3
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
0.5747	Remote Similarity	NPD8099	Discontinued
0.5667	Remote Similarity	NPD8156	Discontinued
0.5269	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