NPASS Compound

Natural Product: NPC30182

Natural Product ID	NPC30182
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Thalifasine
IUPAC Name	(6aS)-8-[4-[[(1S)-5-hydroxy-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl]methyl]phenoxy]-1,2,9,10-tetramethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-3-ol
Synonyms	Thalifasine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL510732
PubChem CID	10372546
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0000381] Aporphines

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 97103 0 0 0 0 0 0 0 0999 V2000 0.5976 3.2899 0.6640 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3825 1.8915 0.6200 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2347 1.1040 -0.1767 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9614 1.1179 -1.5232 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1369 1.8107 -2.0071 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5709 1.5355 -3.3161 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7950 0.3895 -2.3892 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8555 -0.3034 -1.8511 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1269 -0.3498 -0.4759 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2844 0.3720 0.3211 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3984 0.4309 1.7510 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1590 0.0515 2.3603 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5731 -1.1333 2.2317 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6802 -1.3469 2.8402 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2926 -0.3765 3.5422 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6601 0.8930 3.7001 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5454 1.0693 3.1102 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7513 -0.3625 3.9224 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4601 -0.0011 2.5992 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9322 1.2457 2.1147 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.7321 1.3103 0.7096 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3639 2.4308 2.7533 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7878 2.6830 2.2897 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5268 1.4055 2.5827 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9063 0.2006 2.7456 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7837 -0.8922 3.0094 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1358 -0.7345 3.0944 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9029 -1.8017 3.3759 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8601 -3.1009 3.6669 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7131 0.5369 2.9112 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9049 1.5830 2.6603 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4196 2.8758 2.4824 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.1118 0.5974 2.9989 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.9207 0.4569 1.8274 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2196 -1.1346 0.1133 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2090 -1.6431 -0.8292 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1613 -1.2638 -2.2382 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9401 -0.7629 -2.7356 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8775 -0.5034 -4.0877 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7889 0.0245 -4.7503 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8836 1.4546 -5.0457 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0152 -0.7670 -4.8568 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2065 -1.2686 -4.3568 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2858 -1.5179 -3.0058 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5618 -2.0389 -2.4761 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4205 -2.4050 -0.9926 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5881 -1.3609 -0.3590 N 0 0 0 0 0 0 0 0 0 0 0 0 6.7129 -1.3327 1.0536 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2032 -1.4695 -5.2910 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9051 -0.4835 -6.2152 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5958 -1.4144 -7.1913 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3820 3.6298 -0.4138 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1422 3.7943 1.2997 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6518 3.5380 0.9312 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2004 0.5003 -3.6408 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7016 1.3421 -3.1994 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4027 2.2816 -4.0951 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5298 0.3170 -3.3979 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0189 -1.9369 1.6713 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1262 -2.3102 2.7487 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1384 1.6179 4.3167 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0784 2.0189 3.2272 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9539 0.4283 4.6620 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0371 -1.3231 4.3109 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2845 -0.7668 1.8324 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6993 1.1697 0.1883 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3159 2.2757 0.3561 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0894 0.4332 0.3896 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3719 2.3668 3.8631 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6851 3.2786 2.4465 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2095 3.5696 2.7885 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7520 2.8870 1.1835 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3076 -1.8561 3.1376 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0096 -3.3509 4.3637 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7447 -3.8400 2.8365 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7702 -3.4353 4.2981 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4071 2.9935 2.7222 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6534 1.2887 1.7189 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5093 -0.5081 1.9254 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2819 0.3589 0.9512 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7171 -2.0488 0.5858 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6172 -0.4987 0.9525 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1808 -2.7892 -0.7645 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3596 1.9378 -4.1777 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8702 1.8487 -5.2357 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5172 1.5158 -5.9277 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4145 -1.3372 -2.6373 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8296 -2.9752 -3.0090 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4006 -2.3743 -0.5239 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9361 -3.3476 -0.8364 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5525 -0.3807 1.5593 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7610 -1.6301 1.3357 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0803 -2.1264 1.5237 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4136 -2.4235 -5.6479 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9772 -0.9790 -8.0145 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0281 -2.3198 -6.8370 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5422 -1.8257 -7.6488 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 4 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 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 15 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 1 0 27 30 1 0 30 31 2 0 31 32 1 0 30 33 1 0 33 34 1 0 9 35 1 0 35 36 1 0 36 37 1 0 37 38 2 0 38 39 1 0 39 40 1 0 40 41 1 0 39 42 2 0 42 43 1 0 43 44 2 0 44 45 1 0 45 46 1 0 46 47 1 0 47 48 1 0 43 49 1 0 42 50 1 0 50 51 1 0 10 3 1 0 17 12 1 0 25 19 1 0 47 36 1 0 38 8 1 0 31 24 1 0 44 37 1 0 1 52 1 0 1 53 1 0 1 54 1 0 6 55 1 0 6 56 1 0 6 57 1 0 7 58 1 0 13 59 1 0 14 60 1 0 16 61 1 0 17 62 1 0 18 63 1 0 18 64 1 0 19 65 1 6 21 66 1 0 21 67 1 0 21 68 1 0 22 69 1 0 22 70 1 0 23 71 1 0 23 72 1 0 26 73 1 0 29 74 1 0 29 75 1 0 29 76 1 0 32 77 1 0 34 78 1 0 34 79 1 0 34 80 1 0 35 81 1 0 35 82 1 0 36 83 1 6 41 84 1 0 41 85 1 0 41 86 1 0 45 87 1 0 45 88 1 0 46 89 1 0 46 90 1 0 48 91 1 0 48 92 1 0 48 93 1 0 49 94 1 0 51 95 1 0 51 96 1 0 51 97 1 0 M END

Standard InCHIKey	JKZGCTOQBIITDP-VMPREFPWSA-N
Standard InCHI	InChI=1S/C40H46N2O9/c1-41-15-13-23-25(19-30(45-3)37(47-5)34(23)43)28(41)17-21-9-11-22(12-10-21)51-36-27-18-29-32-24(14-16-42(29)2)35(44)40(50-8)39(49-7)33(32)26(27)20-31(46-4)38(36)48-6/h9-12,19-20,28-29,43-44H,13-18H2,1-8H3/t28-,29-/m0/s1
SMILES	COc1c(OC)cc2c(c1Oc1ccc(cc1)C[C@@H]1N(C)CCc3c1cc(OC)c(c3O)OC)C[C@H]1c3c2c(OC)c(c(c3CCN1C)O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	698.32	Volume:	709.969 ? Van der Waals volume.
Dense:	0.984	LogP:	2.892 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.765 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.075 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	37.0
TPSA:	111.55 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	2.0	Rings:	7.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.19	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.201	Fsp³:	0.4
MCE-18:	139.75 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.761	Fluc inhibitor:	0.01 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.701 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.798 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.387

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.239	MDCK Permeability:	-4.859
Pgp-inhibitor:	0.548	Pgp-substrate:	0.825
PAMPA:	0.001 ? 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):	0.0
20% Bioavailability (F20%):	0.611	30% Bioavailability (F30%):	0.726
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	1.0	MRP1:	1.0
Plasma Protein Binding (PPB):	81.607%	Volume Distribution (VD):	-0.112
Fu:	18.729% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.955
OATP1B3 inhibitor:	0.87	BCRP inhibitor:	0.845
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.969	CYP2C8-inhibitor:	0.0
HLM stability:	0.938 ? 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):

6.605

Half-life (T1/2):

1.77

ADMET: Toxicity

hERG Blockers:	0.866	hERG Blockers (10um):	0.865
Human Hepatotoxicity (H-HT):	0.812	Drug-induced Liver Injury (DILI):	0.067
AMES Toxicity:	0.547	Rat Oral Acute Toxicity:	0.723
Maximum Recommended Daily Dose:	0.997	Skin Sensitization:	0.401
Carcinogencity:	0.503	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.932
Drug-induced Neurotoxicity:	0.942	Ototoxicity:	0.797
Hematotoxicity:	0.082	Drug-induced Nephrotoxicity:	0.34
Genotoxicity:	0.978	RPMI-8226 Immunitoxicity:	0.201
A549 Cytotoxicity:	0.766	Hek293 Cytotoxicity:	0.914
BCF:	1.779 ? 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:	4.845 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.727 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.773 ? 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
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	Roots	n.a.	n.a.	PMID[19299148]
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7528786]
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21435	Thalictrum faberi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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	14

Activity Type	# Activity
Cell line	8
Organism	2
Non-molecular	4

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	=	1.3	ug ml-1	PMID[8340925]
NPT1034	Cell line	Lu1	Homo sapiens	ED50	=	2.0	ug ml-1	PMID[8340925]
NPT1851	Cell line	Col2	Homo sapiens	ED50	=	2.1	ug ml-1	PMID[14698152]
NPT91	Cell line	KB	Homo sapiens	ED50	=	4.6	ug ml-1	PMID[14698152]
NPT168	Cell line	P388	Mus musculus	ED50	=	1.2	ug ml-1	PubChem BioAssay data set
NPT762	Cell line	A-431	Homo sapiens	ED50	=	8.2	ug ml-1	PubChem BioAssay data set
NPT858	Cell line	LNCaP	Homo sapiens	ED50	=	3.3	ug ml-1	PubChem BioAssay data set
NPT133	Cell line	ZR-75-1	Homo sapiens	ED50	=	1.2	ug ml-1	PMID[12570385]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	238.0	ng/ml	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	49.3	ng/ml	PubChem BioAssay data set
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	2.4	ug ml-1	PMID[7528786]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	5.7	ug ml-1	PMID[7528786]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	1.6	ug ml-1	PMID[7528786]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	2.2	ug ml-1	PMID[7528786]

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 NPC30182 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	26359
0.1-0.2	22488
0.2-0.3	799
0.3-0.4	134
0.4-0.5	62
0.5-0.6	5
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8734	High Similarity	NPC478963
0.8519	High Similarity	NPC169959
0.7073	Intermediate Similarity	NPC112248
0.6706	Remote Similarity	NPC478964
0.6552	Remote Similarity	NPC302275
0.6456	Remote Similarity	NPC30779
0.6374	Remote Similarity	NPC478965
0.61	Remote Similarity	NPC478973
0.61	Remote Similarity	NPC478972
0.573	Remote Similarity	NPC286119
0.5625	Remote Similarity	NPC239775
0.5347	Remote Similarity	NPC478971
0.5347	Remote Similarity	NPC478970
0.5152	Remote Similarity	NPC473589

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC30182 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4388
0.1-0.2	4699
0.2-0.3	56
0.3-0.4	6
0.4-0.5	1
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