NPASS Compound

Natural Product: NPC153007

Natural Product ID	NPC153007
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(+)-Axillaridine A
IUPAC Name	N-[(5R,8S,9S,10R,13S,14S,17S)-17-[(1S)-1-(dimethylamino)ethyl]-10,13-dimethyl-4-oxo-1,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-yl]benzamide
Synonyms	(+)-Axillaridine A
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL335133
PubChem CID	3004425
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001194] Oxosteroids

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 76 80 0 0 0 0 0 0 0 0999 V2000 -5.4524 -0.3307 -1.9031 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2761 -0.8341 -0.4947 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3026 -0.0432 0.3023 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2287 -0.6670 1.7137 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8154 -1.2856 1.7321 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0972 -0.1873 1.0513 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6411 -0.2881 0.8727 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0603 -0.5429 2.1712 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2830 0.2060 2.4618 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9147 1.0350 1.4093 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3534 0.7761 1.2232 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0069 0.1963 2.1016 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9865 1.2100 -0.0002 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2711 1.8203 -0.9651 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8154 2.0637 -0.7981 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2540 0.9396 0.0490 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5971 -0.3492 -0.6719 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2051 1.0650 0.2910 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0054 1.4439 -0.9010 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4965 1.4525 -0.6296 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9108 0.0413 -0.1978 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5975 -0.8505 -1.3438 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3741 0.9944 -0.1866 N 0 0 0 0 0 0 0 0 0 0 0 0 5.9609 -0.1524 -0.0998 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3971 -0.2505 -0.3124 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1167 0.9020 -0.6081 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4767 0.7993 -0.8071 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0996 -0.4210 -0.7133 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3898 -1.5634 -0.4208 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0249 -1.4698 -0.2195 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2289 -1.2967 0.1959 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5711 -0.8866 0.2037 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.4907 -1.7601 -0.4621 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0984 0.4381 0.4254 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5267 -0.2277 -2.1793 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0091 0.6584 -2.0724 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0329 -1.0227 -2.6651 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0026 -1.9250 -0.5739 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7048 0.9912 0.3910 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0029 -1.4094 1.8716 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2213 0.1611 2.4427 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8402 -2.1710 1.0989 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5045 -1.4613 2.7749 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2812 0.7444 1.6757 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3526 -1.0941 0.1910 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2209 -1.6585 2.2857 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6933 -0.3334 2.9900 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0820 -0.5219 2.8068 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1610 0.8603 3.3782 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8485 2.1368 1.6676 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8121 2.1119 -1.8422 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5939 3.0557 -0.4010 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3645 1.9428 -1.8145 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5066 -0.2285 -1.3298 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7958 -1.1874 -0.0060 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7782 -0.5440 -1.4143 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3620 1.8246 1.0873 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7656 0.8253 -1.7939 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7342 2.4847 -1.1747 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9698 1.7565 -1.5827 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6835 2.1683 0.1888 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1459 -1.8174 -1.3609 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8056 -0.2639 -2.2909 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5408 -1.1030 -1.4309 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5847 1.8382 -0.6716 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0507 1.6928 -1.0390 H 0 0 0 0 0 0 0 0 0 0 0 0 11.1762 -0.5197 -0.8681 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8690 -2.5307 -0.3441 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4245 -2.3533 0.0149 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2656 -1.3508 -0.1522 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5856 -2.6903 0.1677 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1200 -2.0824 -1.4646 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4938 -1.3120 -0.4960 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6291 1.1100 -0.3065 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7499 0.7635 1.4354 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1983 0.4775 0.4414 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 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 11 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 6 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 6 13 23 1 0 23 24 2 3 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 24 31 1 0 2 32 1 0 32 33 1 0 32 34 1 0 21 3 1 0 30 25 1 0 21 6 1 0 18 7 1 0 16 10 1 0 1 35 1 0 1 36 1 0 1 37 1 0 2 38 1 6 3 39 1 1 4 40 1 0 4 41 1 0 5 42 1 0 5 43 1 0 6 44 1 1 7 45 1 6 8 46 1 0 8 47 1 0 9 48 1 0 9 49 1 0 10 50 1 1 14 51 1 0 15 52 1 0 15 53 1 0 17 54 1 0 17 55 1 0 17 56 1 0 18 57 1 1 19 58 1 0 19 59 1 0 20 60 1 0 20 61 1 0 22 62 1 0 22 63 1 0 22 64 1 0 26 65 1 0 27 66 1 0 28 67 1 0 29 68 1 0 30 69 1 0 31 70 1 0 33 71 1 0 33 72 1 0 33 73 1 0 34 74 1 0 34 75 1 0 34 76 1 0 M END

Standard InCHIKey	ZMAOKPMWBVUQPK-IWDJEAQTSA-N
Standard InCHI	InChI=1S/C30H42N2O2/c1-19(32(4)5)22-13-14-23-21-11-12-25-27(33)26(31-28(34)20-9-7-6-8-10-20)16-18-30(25,3)24(21)15-17-29(22,23)2/h6-10,16,19,21-25H,11-15,17-18H2,1-5H3,(H,31,34)/t19-,21-,22+,23-,24-,25-,29+,30+/m0/s1
SMILES	C[C@@H]([C@H]1CC[C@H]2[C@@H]3CC[C@H]4C(=O)C(=CC[C@]4(C)[C@H]3CC[C@]12C)N=C(c1ccccc1)O)N(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.32	Volume:	508.409 ? Van der Waals volume.
Dense:	0.909	LogP:	4.667 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.914 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.623 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	28.0
TPSA:	52.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.424	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.677	Fsp³:	0.667
MCE-18:	113.92 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.687	Fluc inhibitor:	0.49 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.177 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.004 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.004	Promiscuous compounds:	0.065

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.398	MDCK Permeability:	-5.056
Pgp-inhibitor:	0.042	Pgp-substrate:	0.019
PAMPA:	0.162 ? 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%):	0.001	30% Bioavailability (F30%):	0.005
50% Bioavailability (F50%):	0.691

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.992	MRP1:	0.115
Plasma Protein Binding (PPB):	65.986%	Volume Distribution (VD):	0.134
Fu:	31.604% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.594
OATP1B3 inhibitor:	0.798	BCRP inhibitor:	0.041
BSEP inhibitor:	0.02

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.104
CYP2C19-inhibitor:	0.667	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.031
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.404
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.006
HLM stability:	0.011 ? 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):

7.632

Half-life (T1/2):

1.408

ADMET: Toxicity

hERG Blockers:	0.43	hERG Blockers (10um):	0.256
Human Hepatotoxicity (H-HT):	0.939	Drug-induced Liver Injury (DILI):	0.842
AMES Toxicity:	0.28	Rat Oral Acute Toxicity:	0.355
Maximum Recommended Daily Dose:	0.792	Skin Sensitization:	0.99
Carcinogencity:	0.879	Eye Corrosion:	0.0
Eye Irritation:	0.044	Respiratory Toxicity:	0.974
Drug-induced Neurotoxicity:	0.17	Ototoxicity:	0.738
Hematotoxicity:	0.749	Drug-induced Nephrotoxicity:	0.808
Genotoxicity:	0.957	RPMI-8226 Immunitoxicity:	0.031
A549 Cytotoxicity:	0.067	Hek293 Cytotoxicity:	0.56
BCF:	1.014 ? 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:	3.742 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.191 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.674 ? 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
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14584959]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14643329]
NPO26156	Mahurea palustris	Species	Calophyllaceae	Eukaryota	leaves	French Guiana	1996-OCT	PMID[16038535]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9548847]
NPO4994	Pachysandra procumbens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9784163]
NPO25707	Euchaeta russelli	Species	Euchaetidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23047	Streptomyces griseoviridis	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4994	Pachysandra procumbens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26673	Casearia ilicifolia	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26204	Arisaema curvatum	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26204	Arisaema curvatum	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26471	Lenormandia smithiae	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18582	Cosmospora butyri	Species	Nectriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23047	Streptomyces griseoviridis	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO26446	Lecanora frustulosa	Species	Lecanoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26423	Scaevola racemigera	Species	Goodeniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26204	Arisaema curvatum	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26156	Mahurea palustris	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26673	Casearia ilicifolia	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4994	Pachysandra procumbens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26556	Pterocephalus pinardi	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23214	Drosera congolana	Species	Droseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25707	Euchaeta russelli	Species	Euchaetidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26372	Sarcandra hainanensis	Species	Chloranthaceae	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
IC50	4
Ki	2

Activity Type	# Activity
Individual protein	5
Protein complex	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2668	Individual protein	Acetylcholinesterase	Torpedo californica	IC50	=	5200.0	nM	PMID[14584959]
NPT2668	Individual protein	Acetylcholinesterase	Torpedo californica	Ki	=	3030.0	nM	PMID[14584959]
NPT204	Individual protein	Acetylcholinesterase	Homo sapiens	IC50	=	5248.07	nM	PMID[14643329]
NPT3844	Protein complex	Anti-estrogen binding site (AEBS)	Homo sapiens	IC50	=	8000.0	nM	PMID[9784163]
NPT439	Individual protein	Butyrylcholinesterase	Homo sapiens	IC50	=	2490.0	nM	PMID[14584959]
NPT439	Individual protein	Butyrylcholinesterase	Homo sapiens	Ki	=	2150.0	nM	PMID[14584959]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC153007 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	13650
0.1-0.2	35212
0.2-0.3	952
0.3-0.4	24
0.4-0.5	14
0.5-0.6	4
0.6-0.7	2
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	Natural Product ID
0.6923	Remote Similarity	NPC184033
0.6618	Remote Similarity	NPC469958
0.5811	Remote Similarity	NPC109151
0.5385	Remote Similarity	NPC132847
0.5244	Remote Similarity	NPC275839
0.506	Remote Similarity	NPC473922

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC153007 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2441
0.1-0.2	6318
0.2-0.3	389
0.3-0.4	2
0.4-0.5	0
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