NPASS Compound

Natural Product: NPC475666

Natural Product ID	NPC475666
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Conoduramine
IUPAC Name	n.a.
Synonyms	Conoduramine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL510938
PubChem CID	44575153
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002748] Ibogan-type alkaloids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 104112 0 0 0 0 0 0 0 0999 V2000 -8.5854 5.1354 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0923 5.2792 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4702 6.6441 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3525 8.1395 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9987 8.7852 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.8810 10.2806 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6642 8.0787 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9222 7.2617 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2340 5.7945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4171 4.5365 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9499 4.2246 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8351 3.2209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 1.7537 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7062 2.6807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4086 3.6844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0967 5.1517 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3299 5.6152 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2841 -1.5763 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4186 -3.0703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3344 -4.1069 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.1520 -3.9056 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9214 -2.6179 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4212 -2.6403 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1517 -3.9504 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0100 -4.8112 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3823 -5.2381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8825 -5.2157 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5346 -5.7076 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9516 -6.1994 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7848 -1.3913 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6347 -0.6084 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2787 -1.5258 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1422 -0.2992 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6918 5.0416 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3800 6.5088 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1969 7.7668 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1118 6.6656 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7219 5.2953 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3928 4.2916 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.2137 5.1385 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0954 6.3520 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4853 7.7223 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9935 7.8791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4201 7.1832 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5349 6.1796 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2371 8.4412 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7350 8.3627 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2074 3.7704 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4564 6.3566 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3766 3.9609 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9574 6.8398 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8360 8.3613 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9266 9.5253 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7633 11.7760 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3824 10.3461 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3508 10.5797 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7557 9.5759 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7171 8.5337 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5129 5.0106 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5217 3.0401 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7765 3.9025 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4628 2.8151 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5736 1.2902 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1328 3.1443 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6019 6.4101 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8664 7.0418 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7934 4.1886 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7648 0.1828 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8112 -0.1720 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7840 -1.5950 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8911 -2.7841 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3392 -4.2546 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6775 -5.1553 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9152 -2.5059 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5483 -1.1457 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6515 -3.9729 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0708 -5.8718 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5274 -6.2116 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0998 -6.7113 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7840 -5.7722 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2996 -6.6565 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0427 -7.1246 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3547 -4.4516 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3687 -6.6913 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4597 -7.6165 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6126 -4.8529 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0056 0.9274 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3688 -1.1626 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0300 0.7073 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2754 9.2647 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7704 8.2303 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2360 2.7998 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8238 3.7682 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5872 6.1952 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3669 8.9358 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3834 9.2494 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2330 8.2842 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8135 9.8607 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8397 6.8664 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 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 17 18 1 0 18 19 1 0 15 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 27 35 1 1 35 36 2 0 35 37 1 0 37 38 1 0 11 39 1 0 39 40 2 0 40 41 1 0 40 42 1 0 42 43 2 0 43 44 1 0 43 45 1 0 45 46 2 0 46 47 1 0 47 48 2 0 8 49 1 0 49 50 2 0 49 51 1 0 51 52 1 0 9 3 1 0 17 12 1 0 27 21 1 0 44 39 1 0 41 7 1 0 48 42 1 0 22 14 1 0 30 25 1 0 32 26 1 0 1 53 1 0 1 54 1 0 2 55 1 0 3 56 1 0 4 57 1 0 4 58 1 0 6 59 1 0 6 60 1 0 6 61 1 0 7 62 1 6 8 63 1 0 9 64 1 1 10 65 1 0 10 66 1 0 11 67 1 1 13 68 1 0 16 69 1 0 19 70 1 0 19 71 1 0 19 72 1 0 20 73 1 0 23 74 1 0 23 75 1 0 24 76 1 0 24 77 1 0 26 78 1 1 28 79 1 0 28 80 1 0 29 81 1 1 30 82 1 0 30 83 1 0 31 84 1 0 31 85 1 0 32 86 1 1 33 87 1 0 33 88 1 0 34 89 1 0 34 90 1 0 34 91 1 0 38 92 1 0 38 93 1 0 38 94 1 0 41 95 1 0 41 96 1 0 44 97 1 0 45 98 1 0 46 99 1 0 47100 1 0 48101 1 0 52102 1 0 52103 1 0 52104 1 0 M END

Standard InCHIKey	MIMKVHBFKSNSQL-XNUNUSLWSA-N
Standard InCHI	InChI=1S/C43H52N4O5/c1-7-24-15-23-20-43(42(49)52-6)39-27(13-14-47(21-23)40(24)43)29-17-30(36(50-4)19-34(29)45-39)31-16-28-25(8-2)22-46(3)35(37(28)41(48)51-5)18-32-26-11-9-10-12-33(26)44-38(31)32/h8-12,17,19,23-25,28,31,35,37,40,44-45H,2,7,13-16,18,20-22H2,1,3-6H3/t23-,24-,25?,28+,31-,35-,37?,40-,43+/m0/s1
SMILES	C=CC1CN(C)[C@@H]2C([C@@H]1C[C@@H](c1cc3c(cc1OC)[nH]c1c3CCN3[C@@H]4[C@]1(C[C@@H](C3)C[C@@H]4CC)C(=O)OC)c1c(C2)c2c([nH]1)cccc2)C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	704.39	Volume:	734.213 ? Van der Waals volume.
Dense:	0.959	LogP:	4.236 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.259 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.792 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	47.0
TPSA:	99.89 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	2.0	Rings:	10.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.179	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.611	Fsp³:	0.535
MCE-18:	182.788 ? 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:	0.973	Fluc inhibitor:	0.006 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.95 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.674 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.777

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.332	MDCK Permeability:	-5.051
Pgp-inhibitor:	0.733	Pgp-substrate:	0.988
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%):	0.052	30% Bioavailability (F30%):	0.256
50% Bioavailability (F50%):	0.942

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.331	MRP1:	1.0
Plasma Protein Binding (PPB):	96.188%	Volume Distribution (VD):	0.714
Fu:	3.211% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.997
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.034	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.202
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.297 ? 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):

11.177

Half-life (T1/2):

1.613

ADMET: Toxicity

hERG Blockers:	0.912	hERG Blockers (10um):	0.792
Human Hepatotoxicity (H-HT):	0.932	Drug-induced Liver Injury (DILI):	0.988
AMES Toxicity:	0.746	Rat Oral Acute Toxicity:	0.99
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	0.936
Carcinogencity:	0.558	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.999
Drug-induced Neurotoxicity:	0.996	Ototoxicity:	0.981
Hematotoxicity:	0.845	Drug-induced Nephrotoxicity:	0.998
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.407
A549 Cytotoxicity:	0.996	Hek293 Cytotoxicity:	0.97
BCF:	1.628 ? 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:	4.614 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.101 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.771 ? 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
NPO40940	Tabernaemontana chippii	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[4031898]
NPO32727	peschiera laeta	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[7853002]
NPO40940	Tabernaemontana chippii	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	13
MIC	4

Activity Type	# Activity
Cell line	9
Organism	4
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
NPT762	Cell line	A-431	Homo sapiens	ED50	=	3.6	ug ml-1	PMID[22939698]
NPT1851	Cell line	Col2	Homo sapiens	ED50	=	1.1	ug ml-1	PMID[22939698]
NPT2049	Cell line	HT	Homo sapiens	ED50	=	2.0	ug ml-1	PMID[22939698]
NPT91	Cell line	KB	Homo sapiens	ED50	=	8.8	ug ml-1	PMID[22939698]
NPT858	Cell line	LNCaP	Homo sapiens	ED50	=	11.1	ug ml-1	PMID[17067173]
NPT1034	Cell line	Lu1	Homo sapiens	ED50	=	5.3	ug ml-1	PMID[12088429]
NPT147	Cell line	SK-MEL-2	Homo sapiens	ED50	=	1.7	ug ml-1	PMID[12088429]
NPT168	Cell line	P388	Mus musculus	ED50	=	2.6	ug ml-1	PMID[12088429]
NPT133	Cell line	ZR-75-1	Homo sapiens	ED50	=	1.3	ug ml-1	PMID[12088429]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.8	ug ml-1	PMID[7853002]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.6	ug ml-1	PMID[7853002]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	11.7	ug ml-1	PMID[7853002]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	2.6	ug ml-1	PMID[7853002]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	15.0	ug.mL-1	PMID[8277312]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	35.0	ug.mL-1	PMID[8277312]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	110.0	ug.mL-1	PMID[8277312]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	=	400.0	ug.mL-1	PMID[1517739]

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 NPC475666 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	26371
0.1-0.2	22709
0.2-0.3	610
0.3-0.4	90
0.4-0.5	31
0.5-0.6	30
0.6-0.7	8
0.7-0.8	1
0.8-0.85	2
0.85-0.9	0
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9109	High Similarity	NPC485933
0.9109	High Similarity	NPC485970
0.8241	Intermediate Similarity	NPC485885
0.8131	Intermediate Similarity	NPC81939
0.7778	Intermediate Similarity	NPC17437
0.7364	Intermediate Similarity	NPC485969
0.7156	Intermediate Similarity	NPC485963
0.7143	Intermediate Similarity	NPC488883
0.678	Remote Similarity	NPC485922
0.678	Remote Similarity	NPC485886
0.6748	Remote Similarity	NPC485945
0.6748	Remote Similarity	NPC485917
0.6748	Remote Similarity	NPC485954
0.6667	Remote Similarity	NPC485966
0.6392	Remote Similarity	NPC329858
0.6016	Remote Similarity	NPC485968
0.5941	Remote Similarity	NPC473041
0.5917	Remote Similarity	NPC485894
0.5846	Remote Similarity	NPC485919
0.5846	Remote Similarity	NPC485920
0.5794	Remote Similarity	NPC485913
0.5785	Remote Similarity	NPC485964
0.5781	Remote Similarity	NPC488882
0.5781	Remote Similarity	NPC485918
0.5781	Remote Similarity	NPC485915
0.5645	Remote Similarity	NPC485890
0.5631	Remote Similarity	NPC482061
0.5577	Remote Similarity	NPC96321
0.5577	Remote Similarity	NPC111993
0.5577	Remote Similarity	NPC485936
0.5577	Remote Similarity	NPC485937
0.5512	Remote Similarity	NPC485921
0.5512	Remote Similarity	NPC478082
0.5455	Remote Similarity	NPC485935
0.5414	Remote Similarity	NPC471303
0.5372	Remote Similarity	NPC485962
0.5372	Remote Similarity	NPC477065
0.5312	Remote Similarity	NPC485893
0.5263	Remote Similarity	NPC605382
0.5194	Remote Similarity	NPC485891
0.5191	Remote Similarity	NPC485889
0.5185	Remote Similarity	NPC473105
0.5093	Remote Similarity	NPC469928
0.5093	Remote Similarity	NPC330009
0.5074	Remote Similarity	NPC485943
0.5038	Remote Similarity	NPC485892

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475666 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4757
0.1-0.2	4300
0.2-0.3	76
0.3-0.4	15
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
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
0.7217	Intermediate Similarity	NPD8358	Approved

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