NPASS Compound

Natural Product: NPC477065

Natural Product ID	NPC477065
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	19,20-Dihydrotabernamine
IUPAC Name	methyl (1R,12S,14R,15S)-15-ethyl-12-[(1R,15R,17S,18S)-17-ethyl-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4(9),5,7-tetraen-6-yl]-17-methyl-10,17-diazatetracyclo[12.3.1.03,11.04,9]octadeca-3(11),4,6,8-tetraene-18-carboxylate
Synonyms	19,20-Dihydrotabernamine
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44418787
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 3D 96104 0 0 0 0 0 0 0 0999 V2000 9.8435 -1.8442 -0.2340 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5839 -1.2973 -0.8350 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6485 -0.9414 0.3039 C 0 0 1 0 0 0 0 0 0 0 0 0 8.2103 0.0818 1.2367 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2825 1.2792 1.3521 C 0 0 2 0 0 0 0 0 0 0 0 0 5.9024 0.8856 1.8395 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4335 -0.2801 1.0339 C 0 0 2 0 0 0 0 0 0 0 0 0 6.3105 -0.4269 -0.1947 C 0 0 1 0 0 0 0 0 0 0 0 0 6.5224 0.8009 -0.8813 N 0 0 0 0 0 0 0 0 0 0 0 0 7.1099 1.8332 -0.0503 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3935 1.3504 -1.5450 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2900 0.3899 -1.8524 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5097 0.0653 -0.6068 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0090 -0.2249 0.6457 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9747 -0.4552 1.4732 N 0 0 0 0 0 0 0 0 0 0 0 0 1.8199 -0.3186 0.7760 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1561 0.0075 -0.5268 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1827 0.2128 -1.4867 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1415 0.0867 -1.1235 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5169 -0.2372 0.1661 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4874 -0.4313 1.0825 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9548 -0.3756 0.5539 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6863 -1.0430 -0.5664 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9974 -1.6644 -0.1619 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7407 -2.1166 -1.3589 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4698 -0.9881 -2.0050 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3435 -0.3049 -1.0851 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.6168 0.2473 0.0476 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8455 -0.8557 0.7399 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8766 -1.7324 1.3573 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8648 -1.8875 2.6257 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8621 -2.4063 0.6919 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8271 -3.2300 1.3057 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7963 1.4404 -0.3363 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6053 1.6612 0.5251 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4705 0.9576 0.8823 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7403 1.7096 1.7079 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.3398 2.8931 1.9210 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9394 3.9774 2.7061 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7644 5.0895 2.7440 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9396 5.1096 2.0240 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3145 4.0125 1.2483 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5015 2.8852 1.1953 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0771 0.7341 -1.7620 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8369 -2.8324 -2.3547 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6436 -3.2818 -3.5668 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6677 -1.1295 -0.1980 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2189 -2.7443 -0.8018 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6627 -2.2392 0.8039 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7243 -0.4784 -1.5399 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0824 -2.1489 -1.3765 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4150 -1.8528 0.9027 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1632 0.4592 0.8350 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4444 -0.3401 2.2514 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7358 2.0029 2.0382 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2341 1.7537 1.6428 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8960 0.6815 2.9314 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6134 -1.2098 1.6419 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8493 -1.1436 -0.8929 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4022 2.7053 0.0618 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0366 2.2420 -0.4712 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9472 2.2235 -1.0156 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7490 1.7741 -2.5304 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5699 0.9258 -2.5203 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6035 -0.5058 -2.3902 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0046 -0.7040 2.4998 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4995 0.4670 -2.4937 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8808 0.2531 -1.8946 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2311 -0.6885 2.1009 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0086 -1.0589 1.4298 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0224 -1.8982 -0.8948 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7584 -0.3645 -1.4123 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7098 -2.5928 0.4163 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4916 -2.8881 -1.0591 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7980 -0.2883 -2.5530 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1317 -1.4279 -2.7963 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3870 0.5798 0.7724 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2958 -0.3924 1.5889 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4308 -4.1973 1.6509 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2552 -2.6292 2.1506 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6649 -3.4318 0.6085 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4304 1.3591 -1.4091 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4250 2.3528 -0.3613 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8213 1.4559 2.1533 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0098 3.9418 3.2667 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4463 5.9316 3.3579 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5432 6.0036 2.0918 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2384 4.0411 0.6898 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0031 0.9270 -1.1604 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5051 1.6410 -1.9618 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4410 0.2878 -2.7251 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4731 -3.7488 -1.8527 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9599 -2.2394 -2.6515 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7069 -3.4061 -3.2204 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3302 -4.2810 -3.9170 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5396 -2.5151 -4.3485 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 9 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 20 22 1 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 30 31 2 0 30 32 1 0 32 33 1 0 28 34 1 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 1 0 38 39 2 0 39 40 1 0 40 41 2 0 41 42 1 0 42 43 2 0 27 44 1 0 25 45 1 0 45 46 1 0 8 3 1 0 10 5 1 0 14 7 1 0 17 13 1 0 21 16 1 0 36 22 1 0 29 24 1 0 43 35 1 0 43 38 1 0 1 47 1 0 1 48 1 0 1 49 1 0 2 50 1 0 2 51 1 0 3 52 1 1 4 53 1 0 4 54 1 0 5 55 1 1 6 56 1 0 6 57 1 0 7 58 1 1 8 59 1 6 10 60 1 0 10 61 1 0 11 62 1 0 11 63 1 0 12 64 1 0 12 65 1 0 15 66 1 0 18 67 1 0 19 68 1 0 21 69 1 0 22 70 1 1 23 71 1 0 23 72 1 0 24 73 1 1 25 74 1 1 26 75 1 0 26 76 1 0 28 77 1 1 29 78 1 0 33 79 1 0 33 80 1 0 33 81 1 0 34 82 1 0 34 83 1 0 37 84 1 0 39 85 1 0 40 86 1 0 41 87 1 0 42 88 1 0 44 89 1 0 44 90 1 0 44 91 1 0 45 92 1 0 45 93 1 0 46 94 1 0 46 95 1 0 46 96 1 0 M END

Standard InCHIKey	VFOGOXRSGPCZGG-QPFJEDRLSA-N
Standard InCHI	InChI=1S/C40H50N4O2/c1-5-23-15-22-16-32-37-28(13-14-44(20-22)39(23)32)27-12-11-25(17-34(27)42-37)30-18-29-24(6-2)21-43(3)35(36(29)40(45)46-4)19-31-26-9-7-8-10-33(26)41-38(30)31/h7-12,17,22-24,29-30,32,35-36,39,41-42H,5-6,13-16,18-21H2,1-4H3/t22-,23+,24-,29-,30+,32+,35-,36?,39+/m1/s1
SMILES	CC[C@H]1C[C@@H]2C[C@@H]3[C@H]1N(C2)CCC4=C3NC5=C4C=CC(=C5)[C@@H]6C[C@@H]7[C@@H](CN([C@@H](C7C(=O)OC)CC8=C6NC9=CC=CC=C89)C)CC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	618.39	Volume:	661.227 ? Van der Waals volume.
Dense:	0.935	LogP:	4.749 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.585 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.196 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	45.0
TPSA:	64.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	10.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.237	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.327	Fsp³:	0.575
MCE-18:	169.905 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.991	Fluc inhibitor:	0.013 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.902 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.347 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.715

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.215	MDCK Permeability:	-5.104
Pgp-inhibitor:	0.216	Pgp-substrate:	0.904
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%):	0.005	30% Bioavailability (F30%):	0.22
50% Bioavailability (F50%):	0.951

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.721	MRP1:	0.964
Plasma Protein Binding (PPB):	96.018%	Volume Distribution (VD):	0.633
Fu:	4.147% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.978
OATP1B3 inhibitor:	0.962	BCRP inhibitor:	0.987
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.513	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.009
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.025
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.021
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.004 ? 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):

11.594

Half-life (T1/2):

0.937

ADMET: Toxicity

hERG Blockers:	0.932	hERG Blockers (10um):	0.816
Human Hepatotoxicity (H-HT):	0.962	Drug-induced Liver Injury (DILI):	0.887
AMES Toxicity:	0.662	Rat Oral Acute Toxicity:	0.982
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	0.944
Carcinogencity:	0.431	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.999
Drug-induced Neurotoxicity:	0.987	Ototoxicity:	0.986
Hematotoxicity:	0.68	Drug-induced Nephrotoxicity:	0.999
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.324
A549 Cytotoxicity:	0.974	Hek293 Cytotoxicity:	0.897
BCF:	2.392 ? 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:	4.819 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.533 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.177 ? 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
NPO31581	Ervatamia divaricata	Species	n.a.	n.a.	stems and leaves	Xishuangbanna area of Yunnan Province, China	2005-MAY	PMID[17253850]
NPO31581	Ervatamia divaricata	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31581	Ervatamia divaricata	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO31581	Ervatamia divaricata	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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	3

Activity Type	# Activity
Individual protein	1
Cell line	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT204	Individual protein	Acetylcholinesterase	Homo sapiens	IC50	=	227	nM	PMID[22425563]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell line	P388	Mus musculus	IC50	=	430	nM	PMID[17253850]
NPT81	Cell line	A549	Homo sapiens	IC50	=	260	nM	PMID[17253850]

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 NPC477065 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	33214
0.1-0.2	15948
0.2-0.3	521
0.3-0.4	107
0.4-0.5	33
0.5-0.6	20
0.6-0.7	8
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC485962
0.83	Intermediate Similarity	NPC485894
0.8218	Intermediate Similarity	NPC29422
0.7383	Intermediate Similarity	NPC485890
0.7379	Intermediate Similarity	NPC485963
0.7222	Intermediate Similarity	NPC485897
0.7222	Intermediate Similarity	NPC485896
0.6875	Remote Similarity	NPC485921
0.6875	Remote Similarity	NPC478082
0.6491	Remote Similarity	NPC485893
0.6486	Remote Similarity	NPC485964
0.618	Remote Similarity	NPC21605
0.618	Remote Similarity	NPC215538
0.614	Remote Similarity	NPC17437
0.605	Remote Similarity	NPC485889
0.5948	Remote Similarity	NPC485933
0.5948	Remote Similarity	NPC485970
0.5913	Remote Similarity	NPC485969
0.5854	Remote Similarity	NPC478080
0.5785	Remote Similarity	NPC478081
0.5763	Remote Similarity	NPC485957
0.55	Remote Similarity	NPC81939
0.5455	Remote Similarity	NPC485966
0.5372	Remote Similarity	NPC475666
0.5323	Remote Similarity	NPC485959
0.5312	Remote Similarity	NPC189812
0.5312	Remote Similarity	NPC329688
0.5306	Remote Similarity	NPC247735
0.5306	Remote Similarity	NPC472210
0.5306	Remote Similarity	NPC472295
0.5306	Remote Similarity	NPC602103
0.5204	Remote Similarity	NPC329747
0.5161	Remote Similarity	NPC485891
0.5152	Remote Similarity	NPC329793
0.5152	Remote Similarity	NPC600762

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477065 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4957
0.1-0.2	4050
0.2-0.3	132
0.3-0.4	9
0.4-0.5	0
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
0.5152	Remote Similarity	NPD4118	Clinical (unspecified phase)
0.5079	Remote 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