NPASS Compound

Natural Product: NPC302275

Natural Product ID	NPC302275
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Thalifaberine
IUPAC Name	(6aS)-8-[4-[[(1S)-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl]methyl]phenoxy]-1,2,3,9,10-pentamethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
Synonyms	Thalifaberine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL498913
PubChem CID	159246
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 99105 0 0 0 0 0 0 0 0999 V2000 0.1493 -0.2348 4.5729 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8473 0.7441 4.3375 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8701 0.5752 3.3995 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0138 -0.1066 3.7488 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1686 -0.6229 5.0015 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2773 -1.3286 5.4678 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0335 -0.2755 2.8121 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8872 0.2400 1.5478 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7309 0.9355 1.2026 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7095 1.0982 2.1457 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6064 1.7928 1.7128 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5617 1.1693 1.3654 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6259 0.3432 0.2725 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8529 -0.2656 -0.0391 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9686 -0.0486 0.7225 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8702 0.7832 1.8095 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6907 1.4013 2.1533 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2383 -0.6967 0.3729 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9975 0.2339 -0.5641 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2953 0.5216 -1.7691 N 0 0 0 0 0 0 0 0 0 0 0 0 4.4427 1.8852 -2.2114 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4519 -0.4536 -2.7949 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8349 -0.9033 -3.0448 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7934 -0.7430 -1.9379 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3922 -0.1991 -0.7512 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3440 -0.0764 0.2504 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6401 -0.4787 0.0765 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5678 -0.3440 1.0939 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1457 0.2194 2.3192 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0507 -1.0311 -1.1266 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1256 -1.1602 -2.1267 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3772 -1.4427 -1.3044 O 0 0 0 0 0 0 0 0 0 0 0 0 10.8190 -2.0020 -2.5042 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6401 1.6758 -0.0956 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2759 0.8523 -1.1528 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.6618 0.4743 -0.7610 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9061 0.0001 0.5235 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1184 -0.4994 0.8912 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5094 -1.0316 2.0987 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5631 -2.4668 2.2719 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1295 -0.5006 -0.0917 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8897 -0.0210 -1.3677 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6541 0.4694 -1.7150 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4516 0.9759 -3.0922 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2898 1.9540 -3.0643 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1355 1.3713 -2.4664 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.4926 0.3914 -3.3144 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8999 -0.0278 -2.3224 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7324 1.0895 -2.4269 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4045 -0.9817 0.1744 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7621 -2.3152 -0.1120 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1179 -0.9057 5.4195 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4329 -0.7914 3.6637 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0619 0.3292 4.8977 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3127 -2.3019 4.9147 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0940 -1.5839 6.5363 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2281 -0.7836 5.3198 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8856 -0.7696 3.1615 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2406 0.1401 -0.3521 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8507 -0.9028 -0.9044 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7890 0.9310 2.3952 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6121 2.0501 3.0002 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8781 -0.8209 1.2715 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0067 -1.6645 -0.1168 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0584 1.2096 0.0064 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1286 1.9871 -3.2526 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4542 2.2513 -2.0093 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7247 2.4998 -1.6052 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8133 -1.3675 -2.6131 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0010 -0.0123 -3.7329 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2255 -0.3008 -3.9211 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8987 -1.9598 -3.4310 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9940 0.3601 1.1831 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6531 1.1906 2.2059 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0481 0.3749 2.9389 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4464 -0.4651 2.8455 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4126 -1.5894 -3.0843 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7424 -1.3424 -3.3793 H 0 0 0 0 0 0 0 0 0 0 0 0 11.8478 -2.4025 -2.3504 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1846 -2.9033 -2.7048 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2635 2.6255 0.0884 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6293 2.0108 -0.3105 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7209 -0.1569 -1.1023 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0519 -2.6935 3.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0609 -2.9822 1.4605 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6258 -2.7906 2.4502 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3257 1.5075 -3.4856 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1841 0.1714 -3.7982 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5441 2.8859 -2.5304 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0314 2.2294 -4.1050 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1301 -0.5267 -3.4357 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5849 0.0431 -2.7763 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1894 0.7999 -4.2998 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3097 1.9783 -1.9496 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7154 0.8777 -1.9546 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9267 1.3508 -3.4999 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8961 -2.9888 -0.2436 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3325 -2.6971 0.7719 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4385 -2.3855 -0.9900 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 30 32 1 0 32 33 1 0 9 34 1 0 34 35 1 0 35 36 1 0 36 37 2 0 37 38 1 0 38 39 1 0 39 40 1 0 38 41 2 0 41 42 1 0 42 43 2 0 43 44 1 0 44 45 1 0 45 46 1 0 46 47 1 0 42 48 1 0 48 49 1 0 41 50 1 0 50 51 1 0 10 3 1 0 17 12 1 0 25 19 1 0 46 35 1 0 37 8 1 0 31 24 1 0 43 36 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 1 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 31 77 1 0 33 78 1 0 33 79 1 0 33 80 1 0 34 81 1 0 34 82 1 0 35 83 1 6 40 84 1 0 40 85 1 0 40 86 1 0 44 87 1 0 44 88 1 0 45 89 1 0 45 90 1 0 47 91 1 0 47 92 1 0 47 93 1 0 49 94 1 0 49 95 1 0 49 96 1 0 51 97 1 0 51 98 1 0 51 99 1 0 M END

Standard InCHIKey	RRKYSGHTIGWTJQ-CONSDPRKSA-N
Standard InCHI	InChI=1S/C41H48N2O8/c1-42-16-14-24-19-32(44-3)33(45-4)21-27(24)30(42)18-23-10-12-25(13-11-23)51-38-29-20-31-35-26(15-17-43(31)2)37(47-6)41(50-9)40(49-8)36(35)28(29)22-34(46-5)39(38)48-7/h10-13,19,21-22,30-31H,14-18,20H2,1-9H3/t30-,31-/m0/s1
SMILES	COc1c(OC)cc2c(c1Oc1ccc(cc1)C[C@@H]1N(C)CCc3c1cc(OC)c(c3)OC)C[C@H]1c3c2c(OC)c(c(c3CCN1C)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	696.34	Volume:	718.474 ? Van der Waals volume.
Dense:	0.969	LogP:	3.135 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.052 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.408 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	37.0
TPSA:	80.32 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	0.0	Rings:	7.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.163	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.029	Fsp³:	0.415
MCE-18:	136.138 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.828	Fluc inhibitor:	0.057 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.683 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.7 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.379

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.718	MDCK Permeability:	-4.657
Pgp-inhibitor:	0.719	Pgp-substrate:	0.707
PAMPA:	0.0 ? 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%):	0.759	30% Bioavailability (F30%):	0.373
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.999	MRP1:	1.0
Plasma Protein Binding (PPB):	73.521%	Volume Distribution (VD):	0.123
Fu:	23.92% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.32
OATP1B3 inhibitor:	0.746	BCRP inhibitor:	0.909
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.994	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.084
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.745
CYP2B6-substrate:	0.963	CYP2C8-inhibitor:	0.365
HLM stability:	0.783 ? 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):

8.778

Half-life (T1/2):

2.224

ADMET: Toxicity

hERG Blockers:	0.931	hERG Blockers (10um):	0.883
Human Hepatotoxicity (H-HT):	0.792	Drug-induced Liver Injury (DILI):	0.023
AMES Toxicity:	0.495	Rat Oral Acute Toxicity:	0.897
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	0.164
Carcinogencity:	0.53	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.978
Drug-induced Neurotoxicity:	0.993	Ototoxicity:	0.549
Hematotoxicity:	0.043	Drug-induced Nephrotoxicity:	0.449
Genotoxicity:	0.993	RPMI-8226 Immunitoxicity:	0.136
A549 Cytotoxicity:	0.563	Hek293 Cytotoxicity:	0.76
BCF:	2.574 ? 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:	5.114 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.621 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.217 ? 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]
NPO24447	Thalictrum cultratum	Species	Ranunculaceae	Eukaryota	Roots	n.a.	n.a.	PMID[29131616]
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]
NPO24447	Thalictrum cultratum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24447	Thalictrum cultratum	Species	Ranunculaceae	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	14
IC50	2

Activity Type	# Activity
Cell line	10
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	=	2.6	ug ml-1	PMID[7528786]
NPT1034	Cell line	Lu1	Homo sapiens	ED50	=	16.3	ug ml-1	PMID[7528786]
NPT1851	Cell line	Col2	Homo sapiens	ED50	=	1.6	ug ml-1	PMID[7528786]
NPT91	Cell line	KB	Homo sapiens	ED50	=	15.5	ug ml-1	PMID[7528786]
NPT168	Cell line	P388	Mus musculus	ED50	=	1.3	ug ml-1	PMID[7528786]
NPT762	Cell line	A-431	Homo sapiens	ED50	=	4.9	ug ml-1	PMID[7528786]
NPT858	Cell line	LNCaP	Homo sapiens	ED50	=	5.7	ug ml-1	PMID[7528786]
NPT133	Cell line	ZR-75-1	Homo sapiens	ED50	=	3.7	ug ml-1	PMID[7528786]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	7270.0	nM	PMID[29131616]
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	1580.0	nM	PMID[29131616]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	5090.0	ng/ml	PMID[7528786]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	ED50	=	441.0	ng/ml	PMID[7528786]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	5.4	ug ml-1	PMID[7528786]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	4.6	ug ml-1	PMID[7528786]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	1.2	ug ml-1	PMID[7528786]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	4.1	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 NPC302275 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	35028
0.1-0.2	14261
0.2-0.3	335
0.3-0.4	111
0.4-0.5	86
0.5-0.6	25
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8667	High Similarity	NPC478964
0.84	Intermediate Similarity	NPC112248
0.7927	Intermediate Similarity	NPC478965
0.7831	Intermediate Similarity	NPC169959
0.6977	Remote Similarity	NPC478963
0.6629	Remote Similarity	NPC473589
0.6552	Remote Similarity	NPC30182
0.6452	Remote Similarity	NPC478971
0.6452	Remote Similarity	NPC478970
0.6061	Remote Similarity	NPC478973
0.6061	Remote Similarity	NPC478972
0.5955	Remote Similarity	NPC47077
0.5844	Remote Similarity	NPC247639
0.5844	Remote Similarity	NPC25084
0.5517	Remote Similarity	NPC603853
0.5455	Remote Similarity	NPC317439
0.5349	Remote Similarity	NPC276890
0.5342	Remote Similarity	NPC314682
0.5301	Remote Similarity	NPC317272
0.5301	Remote Similarity	NPC268503
0.5287	Remote Similarity	NPC227060
0.5233	Remote Similarity	NPC76682
0.5233	Remote Similarity	NPC10908
0.5233	Remote Similarity	NPC63646
0.5233	Remote Similarity	NPC317145
0.5233	Remote Similarity	NPC198498
0.5233	Remote Similarity	NPC115284
0.5114	Remote Similarity	NPC603603
0.5111	Remote Similarity	NPC480587
0.5067	Remote Similarity	NPC213206
0.5067	Remote Similarity	NPC188163
0.5067	Remote Similarity	NPC328750
0.5056	Remote Similarity	NPC12424
0.5056	Remote Similarity	NPC129518
0.5056	Remote Similarity	NPC251580
0.5053	Remote Similarity	NPC212237

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC302275 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5312
0.1-0.2	3764
0.2-0.3	64
0.3-0.4	5
0.4-0.5	3
0.5-0.6	2
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
0.5233	Remote Similarity	NPD8099	Discontinued
0.5067	Remote Similarity	NPD4664	Clinical (unspecified phase)

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