NPASS Compound

Natural Product: NPC483959

Natural Product ID	NPC483959
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LYIGHNVZRJJMOV-YGVQMNHXSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	76309965
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002755] Aspidospermatan-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 99109 0 0 0 0 0 0 0 0999 V2000 -7.3342 -1.1362 -2.7294 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8963 -0.9891 -2.3583 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7562 -0.7641 -0.8401 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.3507 -1.9588 -0.2131 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6355 -3.0286 0.0546 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1774 -2.9858 -0.3048 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6432 -1.6946 0.0794 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.9409 -1.5493 1.5141 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4191 -0.1273 1.7122 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9952 0.5109 0.3897 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5566 0.8676 0.4399 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3859 0.1119 0.5128 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1274 0.6562 0.6583 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0384 2.0296 0.7351 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1736 2.8187 0.6655 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4255 2.2344 0.5162 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7329 2.8128 0.3125 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.6633 1.7670 0.0958 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9175 1.6924 -0.3377 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6242 0.4294 -0.5273 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6027 2.9444 -0.6320 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0877 4.0767 -0.5031 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9141 2.9019 -1.0868 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6489 4.0751 -1.3951 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1832 2.6687 0.8839 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1001 -0.2131 0.7293 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3214 -0.5403 2.1645 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5739 -0.6932 2.6294 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6793 -0.7345 1.6139 C 0 0 1 0 0 0 0 0 0 0 0 0 4.9572 -0.4052 2.3991 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9172 0.9337 3.0519 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8448 -2.1677 1.1443 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1310 -2.2047 0.3913 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3147 -1.2208 -0.4830 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3156 -0.1789 -0.6926 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3022 -0.7327 -1.6955 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0504 0.0196 -1.3616 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1500 0.4043 0.0325 N 0 0 0 0 0 0 0 0 0 0 0 0 3.4923 0.2206 0.4771 C 0 0 1 0 0 0 0 0 0 0 0 0 5.0256 0.9267 -1.3922 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5917 2.2026 -1.6568 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3943 3.0173 -2.4276 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6027 2.5406 -2.9119 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0158 1.2609 -2.6317 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2236 0.4486 -1.8652 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4200 -0.8720 -1.3279 N 0 0 0 0 0 0 0 0 0 0 0 0 7.4041 3.3690 -3.6905 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1186 -3.2362 0.5888 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9449 -4.1812 1.4269 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3087 -3.2673 -0.1122 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2510 -4.2776 0.0957 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9585 0.5601 2.8746 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3276 -0.6014 -0.5616 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.9415 -1.2986 -1.8018 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5233 -1.9870 -3.4202 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7301 -0.2389 -3.2609 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2437 -1.7845 -2.7196 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5236 -0.0436 -2.8515 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4243 -1.9669 0.0442 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1076 -3.8827 0.5126 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9763 -3.2765 -1.3382 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6821 -3.7383 0.3473 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7789 -2.2090 1.8127 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0604 -1.7928 2.1214 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7855 0.3478 2.4963 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4722 -0.0189 1.9400 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4757 -0.9568 0.4529 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1014 3.8966 0.7274 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9334 3.8355 0.3278 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3928 0.5989 -1.3400 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2328 0.2171 0.3707 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7146 3.8568 -1.1645 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5009 4.3499 -2.4534 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3331 4.8776 -0.6894 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2303 3.5805 1.3221 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7925 -1.1527 0.1791 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3770 -0.8063 2.7138 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8408 -1.2807 3.5579 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8681 -0.5672 1.8172 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9820 -1.1855 3.2147 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0612 1.5648 2.8165 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8555 1.4866 2.8266 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9211 0.8371 4.1788 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0009 -2.7830 2.0702 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0030 -2.5858 0.6162 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2114 -1.8226 -1.6152 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6630 -0.5184 -2.7395 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1756 -0.6315 -1.5639 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9821 0.8976 -2.0338 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8670 1.2202 0.8223 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6596 2.6010 -1.2965 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0826 4.0459 -2.6636 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9767 0.8857 -3.0175 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2516 -1.4612 -1.5407 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0056 4.0618 -3.2525 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4147 -4.4042 1.1779 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0179 -5.2208 -0.4217 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2236 -3.8992 -0.3345 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7475 -0.3885 -1.5016 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 6 3 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 10 9 1 1 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 19 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 14 25 1 0 13 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 1 30 31 1 0 29 32 1 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 1 6 36 37 1 0 37 38 1 0 38 39 1 0 35 40 1 0 40 41 2 0 41 42 1 0 42 43 2 0 43 44 1 0 44 45 2 0 45 46 1 0 43 47 1 0 33 48 1 0 48 49 2 0 48 50 1 0 50 51 1 0 28 52 1 0 10 53 1 0 20 3 1 0 38 26 1 0 45 40 1 0 53 3 1 0 53 7 1 0 18 10 1 0 52 27 1 0 16 11 1 0 39 29 1 0 46 34 1 0 39 35 1 0 1 54 1 0 1 55 1 0 1 56 1 0 2 57 1 0 2 58 1 0 4 59 1 0 5 60 1 0 6 61 1 0 6 62 1 0 8 63 1 0 8 64 1 0 9 65 1 0 9 66 1 0 12 67 1 0 15 68 1 0 17 69 1 0 20 70 1 0 20 71 1 0 24 72 1 0 24 73 1 0 24 74 1 0 25 75 1 0 26 76 1 6 27 77 1 1 28 78 1 1 30 79 1 0 30 80 1 0 31 81 1 0 31 82 1 0 31 83 1 0 32 84 1 0 32 85 1 0 36 86 1 0 36 87 1 0 37 88 1 0 37 89 1 0 39 90 1 1 41 91 1 0 42 92 1 0 44 93 1 0 46 94 1 0 47 95 1 0 51 96 1 0 51 97 1 0 51 98 1 0 53 99 1 6 M END

Standard InCHIKey	LYIGHNVZRJJMOV-YGVQMNHXSA-N
Standard InCHI	InChI=1S/C42H46N4O7/c1-5-39-10-7-13-45-14-11-42(37(39)45)26-17-22(29(48)18-28(26)44-32(42)23(19-39)35(49)51-3)30-31-34(53-31)40(6-2)20-24(36(50)52-4)33-41(12-15-46(30)38(40)41)25-9-8-21(47)16-27(25)43-33/h7-10,16-18,30-31,34,37-38,43-44,47-48H,5-6,11-15,19-20H2,1-4H3/t30-,31+,34+,37+,38+,39+,40-,41+,42+/m1/s1
SMILES	CC[C@]12C=CCN3CC[C@@]4(c5cc(c(cc5NC4=C(C1)C(=O)OC)O)[C@@H]1[C@H]4[C@@H]([C@@]5(CC)CC(=C6[C@]7(CCN1[C@@H]57)c1ccc(cc1N6)O)C(=O)OC)O4)[C@H]23

Calculated Properties

Physi-Chem Properties

Molecular Weight:	718.34	Volume:	717.384 ? Van der Waals volume.
Dense:	1.001	LogP:	2.512 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.554 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.372 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	50.0
TPSA:	136.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	4.0	Rings:	11.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.186	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.601	Fsp³:	0.524
MCE-18:	292.5 ? 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:	0	PAINS Alert:	1
Colloidal aggregators:	0.929	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.692 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.949 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.093

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.736	MDCK Permeability:	-5.223
Pgp-inhibitor:	0.0	Pgp-substrate:	1.0
PAMPA:	0.007 ? 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%):	0.999	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.03	MRP1:	1.0
Plasma Protein Binding (PPB):	94.527%	Volume Distribution (VD):	0.841
Fu:	5.065% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.107
OATP1B3 inhibitor:	0.004	BCRP inhibitor:	0.003
BSEP inhibitor:	0.514

ADMET: Metabolism

CYP1A2-inhibitor:	0.987	CYP1A2-substrate:	0.073
CYP2C19-inhibitor:	0.801	CYP2C19-substrate:	0.12
CYP2C9-inhibitor:	0.016	CYP2C9-substrate:	0.011
CYP2D6-inhibitor:	0.359	CYP2D6-substrate:	0.099
CYP3A4-inhibitor:	0.991	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.92
HLM stability:	0.996 ? 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):

6.883

Half-life (T1/2):

1.306

ADMET: Toxicity

hERG Blockers:	0.064	hERG Blockers (10um):	0.14
Human Hepatotoxicity (H-HT):	0.873	Drug-induced Liver Injury (DILI):	0.823
AMES Toxicity:	0.725	Rat Oral Acute Toxicity:	0.702
Maximum Recommended Daily Dose:	0.983	Skin Sensitization:	0.999
Carcinogencity:	0.317	Eye Corrosion:	0.0
Eye Irritation:	0.005	Respiratory Toxicity:	0.962
Drug-induced Neurotoxicity:	0.738	Ototoxicity:	0.935
Hematotoxicity:	0.905	Drug-induced Nephrotoxicity:	0.987
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.12
A549 Cytotoxicity:	0.912	Hek293 Cytotoxicity:	0.958
BCF:	1.083 ? 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:	4.575 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.941 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.59 ? 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
NPO33137	melodinus suaveolens	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22260257]
NPO33137	melodinus suaveolens	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24274642]

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	5

Activity Type	# Activity
Cell line	4
Non-molecular	1

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
NPT660	Cell line	SW480	Homo sapiens	IC50	=	14400.0	nM	PMID[24274642]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	11600.0	nM	PMID[24274642]
NPT81	Cell line	A549	Homo sapiens	IC50	=	9700.0	nM	PMID[24274642]
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	5500.0	nM	PMID[24274642]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	13800.0	nM	PMID[24274642]

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 NPC483959 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	21387
0.1-0.2	28228
0.2-0.3	141
0.3-0.4	53
0.4-0.5	25
0.5-0.6	17
0.6-0.7	3
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
0.77	Intermediate Similarity	NPC77812
0.77	Intermediate Similarity	NPC303387
0.7283	Intermediate Similarity	NPC203628
0.7179	Intermediate Similarity	NPC483960
0.6667	Remote Similarity	NPC303214
0.6531	Remote Similarity	NPC232600
0.6	Remote Similarity	NPC5630
0.5902	Remote Similarity	NPC256381
0.5758	Remote Similarity	NPC123241
0.5644	Remote Similarity	NPC22476
0.5631	Remote Similarity	NPC119722
0.5545	Remote Similarity	NPC128948
0.5538	Remote Similarity	NPC162473
0.5538	Remote Similarity	NPC41104
0.55	Remote Similarity	NPC469722
0.5462	Remote Similarity	NPC292934
0.5403	Remote Similarity	NPC485928
0.5403	Remote Similarity	NPC477068
0.5392	Remote Similarity	NPC475147
0.5238	Remote Similarity	NPC475133
0.5077	Remote Similarity	NPC601853
0.5076	Remote Similarity	NPC51575
0.5075	Remote Similarity	NPC469734
0.5039	Remote Similarity	NPC608626

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC483959 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5248
0.1-0.2	3871
0.2-0.3	31
0.3-0.4	0
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