13
The
Drug
Research and D e v e l o p m e n t
Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on April 11, 2018 | https://pubs.acs.org Publication Date: December 14, 1978 | doi: 10.1021/bk-1978-0084.ch013
I n f o r m a t i o n S y s t e m of N C I ' s Therapeutics
Chemical
Developmental
Program
SIDNEY RICHMAN, GEORGE F. HAZARD, JR., and ALICE K. KALIKOW Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, MD 20014 The Developmental Therapeutics Program (DTP) in the D i v i s i o n of Cancer Treatment, National Cancer I n s t i t u t e (NCI) i s responsible for all preclinical phases i n the development of cancer t h e r a p e u t i c agents. As one approach to i d e n t i f y i n g leads to such drugs, the DTP (which subsumed the Drug Research and Development Program(1)) acquires drugs, s y n t h e t i c m a t e r i a l s and n a t u r a l products and t e s t s these m a t e r i a l s i n a v a r i e t y of antitumor systems. Since the i n c e p t i o n of the NCI cancer chemotherapy activity i n 1956, some 316,000 chemicals and drugs have been screened i n approximately 4,000,000 animal and in-vitro tests. Currently, 15,000 such m a t e r i a l s are acquired and evaluated y e a r l y . E v o l u t i o n of the System As in other biological screening programs, the supporting chemical i n f o r m a t i o n system (CIS) must p r o v i d e , at a minimum, two basic capabilities: the registration of a c q u i s i t i o n s and access to the data base. The chemical system which was s t a r t e d in 1956 employed a manual r e g i s t r a t i o n procedure based on c a t a l o g i n g compounds by molecular formula and d i f f e r e n t i a t i n g between compounds having the same molecular formula by the systematic chemical name. Systematic names for accessions were maintained on punched paper tape. Substructure searching f o r analogs was based on chemical fragment codes assigned to accessions and an o p t i c a l coincidence system used for r e t r i e v a l . ( 2 ) The second system, used from 1967 through 1974 c o n s i s t e d essentially of three components: the Chemical A b s t r a c t s S e r v i c e (CAS) R e g i s t r y System ( 3 , 4 , 5 ) as adapted f o r NCI p r i v a t e use; CAS' automated batch substructure search procedures (6,7); and computer-generated indexes for identifying substances by systematic name. The passage of the N a t i o n a l Cancer Act of 1971 r e s u l t e d i n an increased y e a r l y a c q u i s i t i o n r a t e which rose i n three years from a
This chapter not subject to U.S. copyright. Published 1978 American Chemical Society Howe et al.; Retrieval of Medicinal Chemical Information ACS Symposium Series; American Chemical Society: Washington, DC, 1978.
13.
RiCHMAN E T A L .
NCfs
Chemical
Information
System
201
l e v e l of 10,000 chemicals and drugs t o 39,000. With a f i l e size of 158,000 substances and complex manual procedures r e q u i r e d d e s p i t e the automated processing of accessions described above, i t was evident t h a t there was need f o r a CIS more responsive t o operational requirements. I n June, 1971 the U n i v e r s i t y o f Pennsylvania, under an NCI c o n t r a c t , began t h e design and implementation of DTP s Drug Research and Development Chemical Information System (DR&D CIS) w i t h a d d i t i o n a l programming support provided by E.I. Dupont de Nemours and Company under subcontract. In J u l y , 1974, t h i s new system was i n s t a l l e d a t t h e Chemical A b s t r a c t s S e r v i c e (CA) which operates the system under an NCI contract. The INVENTORY and SPECIAL STRUCTURAL FEATURE IDENTIFICATION processors were added t o the CIS i n February, 1976 and September, 1977 r e s p e c t i v e l y .
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1
Design C o n s t r a i n t s The c o n s t r a i n t s on the design were t o avoid r e s e a r c h , use e x i s t i n g systems o r programs wherever p o s s i b l e , and be compatible w i t h the CAS environment t o f a c i l i t a t e o p e r a t i o n of t h e e x i s t i n g and planned CAS chemical i n f o r m a t i o n handling techniques. The f o l l o w i n g components were obtained from other systems and were i n t e g r a t e d (sometimes w i t h m o d i f i c a t i o n s ) i n t o the t o t a l system: CAS Data Management System (FIDO) (8.) ; CAS R e g i s t r y I I I (9,10,11); CAS Transaction E d i t o r ; DCRT (NIH) On L i n e S t r u c t u r e Input System f o r query f o r m u l a t i o n (12); General processing u t i l i t i e s and a macro processor from Dupont; U.S. Army CIDS Substructure Ring Screens and I n t e r a c t i v e Search (1_3); CAS A l g o r i t h m i c S t r u c t u r e D i s p l a y (ASD) (14); and CAS On Line S t r u c t u r e Input System (L5) f o r input t o R e g i s t r y . 1
1
I n t e r a c t i o n of the CIS w i t h A c c e s s i o n i n g and Screening 1
F i g u r e 1 o u t l i n e s the r o u t i n e i n t e r a c t i o n of DTP s chemical and drug a c c e s s i o n i n g and screening a c t i v i t i e s (which are h e a v i l y c o n t r a c t supported) w i t h the chemical and b i o l o g i c a l data processing systems. Samples of compounds a r e submitted by s u p p l i e r s or are c o l l e c t e d a t s u p p l i e r s ' s i t e s . Accompanying the samples are data sheets which i n c l u d e the s t r u c t u r a l and s u p p l i e r identification and o c c a s i o n a l l y biological and physical properties. The A c q u i s i t i o n a c t i v i t y weighs and t e m p o r a r i l y s t o r e s t h e sample, prepares and t r a n s m i t s the input documents (which i n c l u d e s t r u c t u r a l and n o n - s t r u c t u r a l data) t o the Chemical Information P r o c e s s i n g a c t i v i t y , and awaits the r e t u r n of 21 a c t i o n and i n f o r m a t i o n a l system outputs. Reports a r e forwarded t o s u p p l i e r s a d v i s i n g them of the accession numbers assigned t o t h e i r submissions o r requesting the replenishment of supply f o r a previous submission t o complete t e s t i n g . Bottle labels are
Howe et al.; Retrieval of Medicinal Chemical Information ACS Symposium Series; American Chemical Society: Washington, DC, 1978.
Howe et al.; Retrieval of Medicinal Chemical Information ACS Symposium Series; American Chemical Society: Washington, DC, 1978.
9
SUPPLIER
Sample with Data Sheet
Inquiry
Reports
Sample with transfer and Shipping Documents
Figure 1.
Test Results
Information on Receipts, Shipments, and Replenishments
DTP STAFF
Shipping Instructions
STORAGE AND DISTRIBUTION
Inquiry
/BIOLOGY \ DATA Ν PROCESSING , SYSTEM / \ (BDPS) / /
Inquiry
Reports
SCREENING SUPPORT
BIOLOGY INFORMATION PROCESSING
JG) SCREENING
Test Results
BIOLOGY \ DATA > PROCESSING . SYSTEM j \ (BDPS) / f
/
Receipt Advice and Return of Samples
Samples with Shipping Documents
Shipping Transactions
'CHEMICAL ^INFORMATION} ^SYSTEM (CIS)/
Interaction of accessioning and screening with data processing
CHEMICAL \ INFORMATION) .SYSTEM (CIS)/
CHEMICAL INFORMATION PROCESSING
Outputs
Inputs
ACQUISITION
Accession Reports and Replenishment Requests
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